Genes

12 pages, 3275 KiB

Open AccessEditor’s ChoiceArticle

Histone Deacetylases (HDAC) Inhibitor—Valproic Acid Sensitizes Human Melanoma Cells to Dacarbazine and PARP Inhibitor

by Małgorzata Drzewiecka, Anna Gajos-Michniewicz, Grażyna Hoser, Dominika Jaśniak, Gabriela Barszczewska-Pietraszek, Przemysław Sitarek, Piotr Czarny, Janusz Piekarski, Maciej Radek, Małgorzata Czyż, Tomasz Skorski and Tomasz Śliwiński

Genes 2023, 14(6), 1295; https://doi.org/10.3390/genes14061295 - 20 Jun 2023

Cited by 10 | Viewed by 3481

Abstract

The inhibition of histone deacetylases (HDACs) holds promise as a potential anti-cancer therapy as histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, the use of a histone deacetylase inhibitor (HDACi) such as the class [...] Read more.

The inhibition of histone deacetylases (HDACs) holds promise as a potential anti-cancer therapy as histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, the use of a histone deacetylase inhibitor (HDACi) such as the class I HDAC inhibitor—valproic acid (VPA) has been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that the use of VPA in combination with talazoparib (BMN-673—PARP1 inhibitor—PARPi) and/or Dacarbazine (DTIC—alkylating agent) resulted in an increased rate of DNA double strand breaks (DSBs) and reduced survival (while not affecting primary melanocytes) and the proliferation of melanoma cells. Furthermore, the pharmacological inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-673. In addition, the inhibition of HDACs causes the sensitization of melanoma cells to DTIV and BMN-673 in melanoma xenografts in vivo. At the mRNA and protein level, the histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study aims to demonstrate that combining an HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is commonly recognized as being among the most aggressive malignant tumors. The findings presented here point to a scenario in which HDACs, via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies. Full article

(This article belongs to the Special Issue DNA Damage Induced by Anti-cancer Agents)

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19 pages, 1200 KiB

Open AccessEditor’s ChoiceArticle

Insights into the Adaptation to High Altitudes from Transcriptome Profiling: A Case Study of an Endangered Species, Kingdonia uniflora

by Man-Li Nong, Xiao-Hui Luo, Li-Xin Zhu, Ya-Nan Zhang, Xue-Yi Dun and Lei Huang

Genes 2023, 14(6), 1291; https://doi.org/10.3390/genes14061291 - 19 Jun 2023

Cited by 4 | Viewed by 1797

Abstract

Kingdonia uniflora is an endangered alpine herb that is distributed along an altitudinal gradient. The unique traits and important phylogenetic position make K. uniflora an ideal model for exploring how endangered plants react to altitude variation. In this study, we sampled nine individuals [...] Read more.

Kingdonia uniflora is an endangered alpine herb that is distributed along an altitudinal gradient. The unique traits and important phylogenetic position make K. uniflora an ideal model for exploring how endangered plants react to altitude variation. In this study, we sampled nine individuals from three representative locations and adopted RNA-seq technology to sequence 18 tissues, aiming to uncover how K. uniflora responded to different altitudes at the gene expression level. We revealed that genes that responded to light stimuli and circadian rhythm genes were significantly enriched in DEGs in the leaf tissue group, while genes that were related to root development and peroxidase activity or involved in the pathways of cutin, suberin, wax biosynthesis, and monoterpenoid biosynthesis were significantly enriched in DEGs in the flower bud tissue group. All of the above genes may play an important role in the response of K. uniflora to various stresses, such as low temperatures and hypoxia in high-altitude environments. Furthermore, we proved that the discrepancy in gene expression patterns between leaf and flower bud tissues varied along the altitudinal gradient. Overall, our findings provide new insights into the adaptation of endangered species to high-altitude environments and further encourage parallel research to focus on the molecular mechanisms of alpine plant evolution. Full article

(This article belongs to the Special Issue Molecular Phylogenetics and Phylogeography of Seed Plants)

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18 pages, 3517 KiB

Open AccessEditor’s ChoiceArticle

Integration of GWAS and RNA-Seq Analysis to Identify SNPs and Candidate Genes Associated with Alkali Stress Tolerance at the Germination Stage in Mung Bean

by Ning Xu, Bingru Chen, Yuxin Cheng, Yufei Su, Mengyuan Song, Rongqiu Guo, Minghai Wang, Kunpeng Deng, Tianjiao Lan, Shuying Bao, Guifang Wang, Zhongxiao Guo and Lihe Yu

Genes 2023, 14(6), 1294; https://doi.org/10.3390/genes14061294 - 19 Jun 2023

Cited by 9 | Viewed by 3592

Abstract

Soil salt-alkalization seriously impacts crop growth and productivity worldwide. Breeding and applying tolerant varieties is the most economical and effective way to address soil alkalization. However, genetic resources for breeders to improve alkali tolerance are limited in mung bean. Here, a genome-wide association [...] Read more.

Soil salt-alkalization seriously impacts crop growth and productivity worldwide. Breeding and applying tolerant varieties is the most economical and effective way to address soil alkalization. However, genetic resources for breeders to improve alkali tolerance are limited in mung bean. Here, a genome-wide association study (GWAS) was performed to detect alkali-tolerant genetic loci and candidate genes in 277 mung bean accessions during germination. Using the relative values of two germination traits, 19 QTLs containing 32 SNPs significantly associated with alkali tolerance on nine chromosomes were identified, and they explained 3.6 to 14.6% of the phenotypic variance. Moreover, 691 candidate genes were mined within the LD intervals containing significant trait-associated SNPs. Transcriptome sequencing of alkali-tolerant accession 132–346 under alkali and control conditions after 24 h of treatment was conducted, and 2565 DEGs were identified. An integrated analysis of the GWAS and DEGs revealed six hub genes involved in alkali tolerance responses. Moreover, the expression of hub genes was further validated by qRT-PCR. These findings improve our understanding of the molecular mechanism of alkali stress tolerance and provide potential resources (SNPs and genes) for the genetic improvement of alkali tolerance in mung bean. Full article

(This article belongs to the Special Issue Genetics and Breeding of Legume Crops)

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21 pages, 5966 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification of the WD40 Gene Family in Tomato (Solanum lycopersicum L.)

by Cunyao Yan, Tao Yang, Baike Wang, Haitao Yang, Juan Wang and Qinghui Yu

Genes 2023, 14(6), 1273; https://doi.org/10.3390/genes14061273 - 15 Jun 2023

Cited by 16 | Viewed by 4059

Abstract

WD40 proteins are a superfamily of regulatory proteins widely found in eukaryotes that play an important role in regulating plant growth and development. However, the systematic identification and characterization of WD40 proteins in tomato (Solanum lycopersicum L.) have not been reported. In [...] Read more.

WD40 proteins are a superfamily of regulatory proteins widely found in eukaryotes that play an important role in regulating plant growth and development. However, the systematic identification and characterization of WD40 proteins in tomato (Solanum lycopersicum L.) have not been reported. In the present study, we identified 207 WD40 genes in the tomatoes genome and analyzed their chromosomal location, gene structure and evolutionary relationships. A total of 207 tomato WD40 genes were classified by structural domain and phylogenetic tree analyses into five clusters and 12 subfamilies and were found to be unevenly distributed across the 12 tomato chromosomes. We identified six tandem duplication gene pairs and 24 segmental duplication pairs in the WD40 gene family, with segmental duplication being the major mode of expansion in tomatoes. Ka/Ks analysis revealed that paralogs and orthologs of WD40 family genes underwent mainly purifying selection during the evolutionary process. RNA-seq data from different tissues and developmental periods of tomato fruit development showed tissue-specific expression of WD40 genes. In addition, we constructed four coexpression networks according to the transcriptome and metabolome data for WD40 proteins involved in fruit development that may be related to total soluble solid formation. The results provide a comprehensive overview of the tomato WD40 gene family and will provide valuable information for the validation of the function of tomato WD40 genes in fruit development. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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17 pages, 3936 KiB

Open AccessEditor’s ChoiceArticle

Comparative Transcriptome Analysis Reveals the Effect of Lignin on Storage Roots Formation in Two Sweetpotato (Ipomoea batatas (L.) Lam.) Cultivars

by Taifeng Du, Zhen Qin, Yuanyuan Zhou, Lei Zhang, Qingmei Wang, Zongyun Li and Fuyun Hou

Genes 2023, 14(6), 1263; https://doi.org/10.3390/genes14061263 - 14 Jun 2023

Cited by 8 | Viewed by 2176

Abstract

Sweet potato (Ipomoea batatas (L.) Lam.) is one of the most important crops with high storage roots yield. The formation and expansion rate of storage root (SR) plays a crucial role in the production of sweet potato. Lignin affects the SR formation; [...] Read more.

Sweet potato (Ipomoea batatas (L.) Lam.) is one of the most important crops with high storage roots yield. The formation and expansion rate of storage root (SR) plays a crucial role in the production of sweet potato. Lignin affects the SR formation; however, the molecular mechanisms of lignin in SR development have been lacking. To reveal the problem, we performed transcriptome sequencing of SR harvested at 32, 46, and 67 days after planting (DAP) to analyze two sweet potato lines, Jishu25 and Jishu29, in which SR expansion of Jishu29 was early and had a higher yield. A total of 52,137 transcripts and 21,148 unigenes were obtained after corrected with Hiseq2500 sequencing. Through the comparative analysis, 9577 unigenes were found to be differently expressed in the different stages in two cultivars. In addition, phenotypic analysis of two cultivars, combined with analysis of GO, KEGG, and WGCNA showed the regulation of lignin synthesis and related transcription factors play a crucial role in the early expansion of SR. The four key genes swbp1, swpa7, IbERF061, and IbERF109 were proved as potential candidates for regulating lignin synthesis and SR expansion in sweet potato. The data from this study provides new insights into the molecular mechanisms underlying the impact of lignin synthesis on the formation and expansion of SR in sweet potatoes and proposes several candidate genes that may affect sweet potato yield. Full article

(This article belongs to the Special Issue Genetics and Genomics of Polyploid Plants)

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15 pages, 3169 KiB

Open AccessEditor’s ChoiceArticle

Genomic Landscape of Copy Number Variations and Their Associations with Climatic Variables in the World’s Sheep

by Hosein Salehian-Dehkordi, Jia-Hui Huang, Nasrollah Pirany, Hossein Mehrban, Xiao-Yang Lv, Wei Sun, Ali Esmailizadeh and Feng-Hua Lv

Genes 2023, 14(6), 1256; https://doi.org/10.3390/genes14061256 - 13 Jun 2023

Cited by 9 | Viewed by 3190

Abstract

Sheep show characteristics of phenotypic diversity and adaptation to diverse climatic regions. Previous studies indicated associations between copy number variations (CNVs) and climate-driven adaptive evolution in humans and other domestic animals. Here, we constructed a genomic landscape of CNVs (n = 39,145) [...] Read more.

Sheep show characteristics of phenotypic diversity and adaptation to diverse climatic regions. Previous studies indicated associations between copy number variations (CNVs) and climate-driven adaptive evolution in humans and other domestic animals. Here, we constructed a genomic landscape of CNVs (n = 39,145) in 47 old autochthonous populations genotyped at a set of high-density (600 K) SNPs to detect environment-driven signatures of CNVs using a multivariate regression model. We found 136 deletions and 52 duplications that were significantly (P_adj. < 0.05) associated with climatic variables. These climate-mediated selective CNVs are involved in functional candidate genes for heat stress and cold climate adaptation (e.g., B3GNTL1, UBE2L3, and TRAF2), coat and wool-related traits (e.g., TMEM9, STRA6, RASGRP2, and PLA2G3), repairing damaged DNA (e.g., HTT), GTPase activity (e.g., COPG), fast metabolism (e.g., LMF2 and LPIN3), fertility and reproduction (e.g., SLC19A1 and CCDC155), growth-related traits (e.g., ADRM1 and IGFALS), and immune response (e.g., BEGAIN and RNF121) in sheep. In particular, we identified significant (P_adj. < 0.05) associations between probes in deleted/duplicated CNVs and solar radiation. Enrichment analysis of the gene sets among all the CNVs revealed significant (P_adj. < 0.05) enriched gene ontology terms and pathways related to functions such as nucleotide, protein complex, and GTPase activity. Additionally, we observed overlapping between the CNVs and 140 known sheep QTLs. Our findings imply that CNVs can serve as genomic markers for the selection of sheep adapted to specific climatic conditions. Full article

(This article belongs to the Special Issue Genetics and Breeding in Sheep and Goats)

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15 pages, 1121 KiB

Open AccessEditor’s ChoiceSystematic Review

Possible Effects of Uremic Toxins p-Cresol, Indoxyl Sulfate, p-Cresyl Sulfate on the Development and Progression of Colon Cancer in Patients with Chronic Renal Failure

by Rossella Di Paola, Ananya De, Raafiah Izhar, Marianna Abate, Silvia Zappavigna, Anna Capasso, Alessandra F. Perna, Antonella La Russa, Giovambattista Capasso, Michele Caraglia and Mariadelina Simeoni

Genes 2023, 14(6), 1257; https://doi.org/10.3390/genes14061257 - 13 Jun 2023

Cited by 21 | Viewed by 4128

Abstract

Chronic kidney disease (CKD) induces several systemic effects, including the accumulation and production of uremic toxins responsible for the activation of various harmful processes. Gut dysbiosis has been widely described in CKD patients, even in the early stages of the disease. The abundant [...] Read more.

Chronic kidney disease (CKD) induces several systemic effects, including the accumulation and production of uremic toxins responsible for the activation of various harmful processes. Gut dysbiosis has been widely described in CKD patients, even in the early stages of the disease. The abundant discharge of urea and other waste substances into the gut favors the selection of an altered intestinal microbiota in CKD patients. The prevalence of bacteria with fermentative activity leads to the release and accumulation in the gut and in the blood of several substances, such as p-Cresol (p-C), Indoxyl Sulfate (IS) and p-Cresyl Sulfate (p-CS). Since these metabolites are normally eliminated in the urine, they tend to accumulate in the blood of CKD patients proportionally to renal impairment. P-CS, IS and p-C play a fundamental role in the activation of various pro-tumorigenic processes, such as chronic systemic inflammation, the increase in the production of free radicals and immune dysfunction. An up to two-fold increase in the incidence of colon cancer development in CKD has been reported in several studies, although the pathogenic mechanisms explaining this compelling association have not yet been described. Based on our literature review, it appears likely the hypothesis of a role of p-C, IS and p-CS in colon cancer development and progression in CKD patients. Full article

(This article belongs to the Special Issue From Genetic to Molecular Basis of Kidney Damage)

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12 pages, 2406 KiB

Open AccessEditor’s ChoiceArticle

Properties of INDETERMINATE DOMAIN Proteins from Physcomitrium patens: DNA-Binding, Interaction with GRAS Proteins, and Transcriptional Activity

by Saiful Islam Khan, Ren Yamada, Ryoichi Shiroma, Tatsuki Abe and Akiko Kozaki

Genes 2023, 14(6), 1249; https://doi.org/10.3390/genes14061249 - 11 Jun 2023

Cited by 1 | Viewed by 3687

Abstract

INDETERMINATE DOMAIN (IDD) proteins are plant-specific transcription factors that interact with GRAS proteins, such as DELLA and SHORT ROOT (SHR), to regulate target genes. The combination of IDD and DELLA proteins regulates genes involved in gibberellic acid (GA) synthesis and GA signaling, whereas [...] Read more.

INDETERMINATE DOMAIN (IDD) proteins are plant-specific transcription factors that interact with GRAS proteins, such as DELLA and SHORT ROOT (SHR), to regulate target genes. The combination of IDD and DELLA proteins regulates genes involved in gibberellic acid (GA) synthesis and GA signaling, whereas the combination of IDD with the complex of SHR and SCARECROW, another GRAS protein, regulates genes involved in root tissue formation. Previous bioinformatic research identified seven IDDs, two DELLA, and two SHR genes in Physcomitrium patens, a model organism for non-vascular plants (bryophytes), which lack a GA signaling pathway and roots. In this study, DNA-binding properties and protein–protein interaction of IDDs from P. patens (PpIDD) were analyzed. Our results showed that the DNA-binding properties of PpIDDs were largely conserved between moss and seed plants. Four PpIDDs showed interaction with Arabidopsis DELLA (AtDELLA) proteins but not with PpDELLAs, and one PpIDD showed interaction with PpSHR but not with AtSHR. Moreover, AtIDD10 (JACKDAW) interacted with PpSHR but not with PpDELLAs. Our results indicate that DELLA proteins have modified their structure to interact with IDD proteins during evolution from moss lineage to seed plants, whereas the interaction of IDD and SHR was already present in moss lineage. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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14 pages, 2987 KiB

Open AccessEditor’s ChoiceCase Report

Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome

by Anna Douka, Lambros Goutzanis, Dimitrios Vlachakis, George P. Chrousos and Christos Yapijakis

Genes 2023, 14(6), 1246; https://doi.org/10.3390/genes14061246 - 10 Jun 2023

Cited by 2 | Viewed by 3509

Abstract

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the TP63 gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical [...] Read more.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the TP63 gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical AEC case of a four-year-old girl with extensive skin erosions and erythroderma of the scalp and the trunk, and to a lesser extent of the limbs, nail dystrophy on the fingers and toes, xerophthalmia, a high-arched palate, oligodontia, and hypohidrosis. Mutation analysis of the TP63 gene detected a de novo missense mutation in exon 14 (c.1799G>T; p.Gly600Val). We discuss the phenotype–genotype correlation by presenting the clinical features of AEC in the patient, and the effect of the detected mutation in p63 structure and function using protein structural modeling, in view of similar cases in the literature. We performed a molecular modeling study in order to link the effect on the protein structure level of the missense mutation G600V. We noted that the introduction of the bulkier Valine residue in place of the slim Glycine residue caused a significantly altered 3D conformational arrangement of that protein region, pushing away the adjacent antiparallel α helix. We propose that the introduced locally altered structure of the G600V mutant p63 has a significant functional effect on specific protein–protein interactions, thus affecting the clinical phenotype. Full article

(This article belongs to the Special Issue Head and Neck Genetics)

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12 pages, 750 KiB

Open AccessEditor’s ChoiceArticle

Success and Pitfalls of Genetic Testing in Undiagnosed Diseases: Whole Exome Sequencing and Beyond

by Valeria Barili, Enrico Ambrosini, Vera Uliana, Melissa Bellini, Giulia Vitetta, Davide Martorana, Ilenia Rita Cannizzaro, Antonietta Taiani, Erika De Sensi, Patrizia Caggiati, Sarah Hilton, Siddharth Banka and Antonio Percesepe

Genes 2023, 14(6), 1241; https://doi.org/10.3390/genes14061241 - 10 Jun 2023

Cited by 6 | Viewed by 3491

Abstract

Novel approaches to uncover the molecular etiology of neurodevelopmental disorders (NDD) are highly needed. Even using a powerful tool such as whole exome sequencing (WES), the diagnostic process may still prove long and arduous due to the high clinical and genetic heterogeneity of [...] Read more.

Novel approaches to uncover the molecular etiology of neurodevelopmental disorders (NDD) are highly needed. Even using a powerful tool such as whole exome sequencing (WES), the diagnostic process may still prove long and arduous due to the high clinical and genetic heterogeneity of these conditions. The main strategies to improve the diagnostic rate are based on family segregation, re-evaluation of the clinical features by reverse-phenotyping, re-analysis of unsolved NGS-based cases and epigenetic functional studies. In this article, we described three selected cases from a cohort of patients with NDD in which trio WES was applied, in order to underline the typical challenges encountered during the diagnostic process: (1) an ultra-rare condition caused by a missense variant in MEIS2, identified through the updated Solve-RD re-analysis; (2) a patient with Noonan-like features in which the NGS analysis revealed a novel variant in NIPBL causing Cornelia de Lange syndrome; and (3) a case with de novo variants in genes involved in the chromatin-remodeling complex, for which the study of the epigenetic signature excluded a pathogenic role. In this perspective, we aimed to (i) provide an example of the relevance of the genetic re-analysis of all unsolved cases through network projects on rare diseases; (ii) point out the role and the uncertainties of the reverse phenotyping in the interpretation of the genetic results; and (iii) describe the use of methylation signatures in neurodevelopmental syndromes for the validation of the variants of uncertain significance. Full article

(This article belongs to the Section Genetic Diagnosis)

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16 pages, 3618 KiB

Open AccessEditor’s ChoiceArticle

The Role of Chromatin Assembly Factors in Induced Mutagenesis at Low Levels of DNA Damage

by Tatiyana A. Evstyukhina, Elena A. Alekseeva, Vyacheslav T. Peshekhonov, Irina I. Skobeleva, Dmitriy V. Fedorov and Vladimir G. Korolev

Genes 2023, 14(6), 1242; https://doi.org/10.3390/genes14061242 - 10 Jun 2023

Cited by 4 | Viewed by 1697

Abstract

The problem of low-dose irradiation has been discussed in the scientific literature for several decades, but it is impossible to come to a generally accepted conclusion about the presence of any specific features of low-dose irradiation in contrast to acute irradiation. We were [...] Read more.

The problem of low-dose irradiation has been discussed in the scientific literature for several decades, but it is impossible to come to a generally accepted conclusion about the presence of any specific features of low-dose irradiation in contrast to acute irradiation. We were interested in the effect of low doses of UV radiation on the physiological processes, including repair processes in cells of the yeast Saccharomyces cerevisiae, in contrast to high doses of radiation. Cells utilize excision repair and DNA damage tolerance pathways without significant delay of the cell cycle to address low levels of DNA damage (such as spontaneous base lesions). For genotoxic agents, there is a dose threshold below which checkpoint activation is minimal despite the measurable activity of the DNA repair pathways. Here we report that at ultra-low levels of DNA damage, the role of the error-free branch of post-replicative repair in protection against induced mutagenesis is key. However, with an increase in the levels of DNA damage, the role of the error-free repair branch is rapidly decreasing. We demonstrate that with an increase in the amount of DNA damage from ultra-small to high, asf1Δ-specific mutagenesis decreases catastrophically. A similar dependence is observed for mutants of gene-encoding subunits of the NuB4 complex. Elevated levels of dNTPs caused by the inactivation of the SML1 gene are responsible for high spontaneous reparative mutagenesis. The Rad53 kinase plays a key role in reparative UV mutagenesis at high doses, as well as in spontaneous repair mutagenesis at ultra-low DNA damage levels. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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17 pages, 9587 KiB

Open AccessEditor’s ChoiceArticle

Estimation of DNA Degradation in Archaeological Human Remains

by Antonella Bonfigli, Patrizia Cesare, Anna Rita Volpe, Sabrina Colafarina, Alfonso Forgione, Massimo Aloisi, Osvaldo Zarivi and Anna Maria Giuseppina Poma

Genes 2023, 14(6), 1238; https://doi.org/10.3390/genes14061238 - 9 Jun 2023

Cited by 4 | Viewed by 3166

Abstract

The evaluation of the integrity and quantity of DNA extracted from archaeological human remains is a fundamental step before using the latest generation sequencing techniques in the study of evolutionary processes. Ancient DNA is highly fragmented and chemically modified; therefore, the present study [...] Read more.

The evaluation of the integrity and quantity of DNA extracted from archaeological human remains is a fundamental step before using the latest generation sequencing techniques in the study of evolutionary processes. Ancient DNA is highly fragmented and chemically modified; therefore, the present study aims to identify indices that can allow the identification of potentially amplifiable and sequenceable DNA samples, reducing failures and research costs. Ancient DNA was extracted from five human bone remains from the archaeological site of Amiternum L’Aquila, Italy dating back to the 9th–12th century and was compared with standard DNA fragmented by sonication. Given the different degradation kinetics of mitochondrial DNA compared to nuclear DNA, the mitochondrially encoded 12s RNA and 18s ribosomal RNA genes were taken into consideration; fragments of various sizes were amplified in qPCR and the size distribution was thoroughly investigated. DNA damage degree was evaluated by calculating damage frequency (λ) and the ratio between the amount of the different fragments and that of the smallest fragment (Q). The results demonstrate that both indices were found to be suitable for identifying, among the samples tested, those less damaged and suitable for post-extraction analysis; mitochondrial DNA is more damaged than nuclear, in fact, amplicons up to 152 bp and 253 bp, respectively are obtained. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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16 pages, 4156 KiB

Open AccessEditor’s ChoiceArticle

Comparative Mitochondrial Genomes between the Genera Amiota and Phortica (Diptera: Drosophilidae) with Evolutionary Insights into D-Loop Sequence Variability

by Caihong Zhang, Yalian Wang, Hongwei Chen and Jia Huang

Genes 2023, 14(6), 1240; https://doi.org/10.3390/genes14061240 - 9 Jun 2023

Cited by 3 | Viewed by 1715

Abstract

To address the limited number of mitochondrial genomes (mitogenomes) in the subfamily Steganinae (Diptera: Drosophilidae), we assembled 12 complete mitogenomes for six representative species in the genus Amiota and six representative species in the genus Phortica. We performed a series of comparative [...] Read more.

To address the limited number of mitochondrial genomes (mitogenomes) in the subfamily Steganinae (Diptera: Drosophilidae), we assembled 12 complete mitogenomes for six representative species in the genus Amiota and six representative species in the genus Phortica. We performed a series of comparative and phylogenetic analyses for these 12 Steganinae mitogenomes, paying special attention to the commonalities and differences in the D-loop sequences. Primarily determined by the lengths of the D-loop regions, the sizes of the Amiota and Phortica mitogenomes ranged from 16,143–16,803 bp and 15,933–16,290 bp, respectively. Our results indicated that the sizes of genes and intergenic nucleotides (IGNs), codon usage and amino acid usage, compositional skewness levels, evolutionary rates of protein-coding genes (PCGs), and D-loop sequence variability all showed unambiguous genus-specific characteristics and provided novel insights into the evolutionary implications between and within Amiota and Phortica. Most of the consensus motifs were found downstream of the D-loop regions, and some of them showed distinct genus-specific patterns. In addition, the D-loop sequences were phylogenetically informative as the data sets of PCGs and/or rRNAs, especially within the genus Phortica. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals)

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17 pages, 4000 KiB

Open AccessEditor’s ChoiceArticle

Vitrification with Dimethyl Sulfoxide Induces Transcriptomic Alteration of Gene and Transposable Element Expression in Immature Human Oocytes

by Ashley Wiltshire, Renata Schaal, Fang Wang, Tiffany Tsou, Wilson McKerrow and David Keefe

Genes 2023, 14(6), 1232; https://doi.org/10.3390/genes14061232 - 8 Jun 2023

Cited by 9 | Viewed by 2757

Abstract

Despite substantial advancements in the field of cryobiology, oocyte and embryo cryopreservation still compromise developmental competence. Furthermore, dimethyl sulfoxide (DMSO), one of the most commonly used cryoprotectants, has been found to exert potent effects on the epigenetic landscape of cultured human cells, as [...] Read more.

Despite substantial advancements in the field of cryobiology, oocyte and embryo cryopreservation still compromise developmental competence. Furthermore, dimethyl sulfoxide (DMSO), one of the most commonly used cryoprotectants, has been found to exert potent effects on the epigenetic landscape of cultured human cells, as well as mouse oocytes and embryos. Little is known about its impact on human oocytes. Additionally, few studies investigate the effects of DMSO on transposable elements (TE), the control of which is essential for the maintenance of genomic instability. The objective of this study was to investigate the impact of vitrification with DMSO-containing cryoprotectant on the transcriptome, including on TEs, of human oocytes. Twenty-four oocytes at the GV stage were donated by four healthy women undergoing elective oocyte cryopreservation. Oocytes were paired such that half from each patient were vitrified with DMSO-containing cryoprotectant (Vitrified Cohort), while the other half were snap frozen in phosphate buffer, unexposed to DMSO (Non-Vitrified Cohort). All oocytes underwent RNA sequencing via a method with high fidelity for single cell analysis, and which allows for the analysis of TE expression through Switching Mechanism at the 5′-end of the RNA Transcript sequencing 2 (SMARTseq2), followed by functional enrichment analysis. Of the 27,837 genes identified by SMARTseq2, 7331 (26.3%) were differentially expressed (p < 0.05). There was a significant dysregulation of genes involved in chromatin and histone modification. Mitochondrial function, as well as the Wnt, insulin, mTOR, HIPPO, and MAPK signaling pathways were also altered. The expression of TEs was positively correlated with the expression of PIWIL2, DNMT3A, and DNMT3B, and negatively correlated with age. These findings suggest that the current standard process of oocyte vitrification, involving DMSO-containing cryoprotectant, induces significant transcriptome changes, including those involving TEs. Full article

(This article belongs to the Special Issue Genetics and Genomics of Female Reproduction)

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11 pages, 1322 KiB

Open AccessEditor’s ChoiceArticle

The Complete Mitochondrial Genome of the Freshwater Fish Onychostoma ovale (Cypriniformes, Cyprinidae): Genome Characterization and Phylogenetic Analysis

by Renyi Zhang, Tingting Zhu and Qi Luo

Genes 2023, 14(6), 1227; https://doi.org/10.3390/genes14061227 - 6 Jun 2023

Cited by 12 | Viewed by 3846

Abstract

In this study, we sequenced and characterized the complete mitochondrial genome (mitogenome) of Onychostoma ovale. The mitogenome of O. ovale was 16,602 bp in length with 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a control [...] Read more.

In this study, we sequenced and characterized the complete mitochondrial genome (mitogenome) of Onychostoma ovale. The mitogenome of O. ovale was 16,602 bp in length with 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a control region. The nucleotide composition of the O. ovale mitogenome was 31.47% A, 24.07% T, 15.92% G, and 28.54% C, with a higher A + T content (55.54%) than G + C content (44.46%). All PCGs began with the standard ATG codon, except for the cytochrome c oxidase subunit 1 (COX1) gene and the NADH dehydrogenase 3 (ND3) gene with GTG, while six PCGs ended with incomplete termination codons (TA or T). The Ka/Ks ratios of 13 PCGs were all less than one, indicating that they were under purifying selection. All tRNA genes were folded into the typical cloverleaf secondary structures with the exception of tRNA^Ser(AGY), whose dihydrouridine (DHU) arm was absent. The phylogenetic trees showed that Onychostoma and Acrossocheilus were classified into three clades. There was a mosaic relationship between Onychostoma and Acrossocheilus. Moreover, the phylogenetic tree analysis showed that O. rarum was the closest species to O. ovale. This study can provide a useful resource for further phylogeny and population genetic analyses of Onychostoma and Acrossocheilus. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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13 pages, 1979 KiB

Open AccessEditor’s ChoiceArticle

Metagenomics Reveals Specific Microbial Features in Males with Semen Alterations

by Iolanda Veneruso, Federica Cariati, Carlo Alviggi, Lucio Pastore, Rossella Tomaiuolo and Valeria D’Argenio

Genes 2023, 14(6), 1228; https://doi.org/10.3390/genes14061228 - 6 Jun 2023

Cited by 13 | Viewed by 2379

Abstract

Infertility incidence is rising worldwide, with male infertility accounting for about 50% of cases. To date, several factors have been associated with male infertility; in particular, it has been suggested that semen microbiota may play a role. Here, we report the NGS-based analyses [...] Read more.

Infertility incidence is rising worldwide, with male infertility accounting for about 50% of cases. To date, several factors have been associated with male infertility; in particular, it has been suggested that semen microbiota may play a role. Here, we report the NGS-based analyses of 20 semen samples collected from men with (Case) and without (Control) semen alterations. Genomic DNA was extracted from each collected sample, and a specific PCR was carried out to amplify the V4-V6 regions of the 16S rRNA. Sequence reactions were carried out on the MiSeq and analyzed by specific bioinformatic tools. We found a reduced richness and evenness in the Case versus the Control group. Moreover, specific genera, the Mannheimia, the Escherichia_Shigella, and the Varibaculum, were significantly increased in the Case compared to the Control group. Finally, we highlighted a correlation between the microbial profile and semen hyperviscosity. Even if further studies are required on larger groups of subjects to confirm these findings and explore mechanistic hypotheses, our results confirm the correlation between semen features and seminal microbiota. These data, in turn, may open the way to the possible use of semen microbiota as an attractive target for developing novel strategies for infertility management. Full article

(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)

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11 pages, 4522 KiB

Open AccessEditor’s ChoiceCommunication

Efficient and Specific Generation of MSTN-Edited Hu Sheep Using C-CRISPR

by Rihong Guo, Huili Wang, Chunhua Meng, Hongbing Gui, Yinxia Li, Fang Chen, Chenjian Zhang, Han Zhang, Qiang Ding, Jianli Zhang, Jun Zhang, Yong Qian, Jifeng Zhong and Shaoxian Cao

Genes 2023, 14(6), 1216; https://doi.org/10.3390/genes14061216 - 2 Jun 2023

Cited by 10 | Viewed by 4373

Abstract

Hu sheep, an indigenous breed in China known for its high fecundity, are being studied to improve their growth and carcass traits. MSTN is a negative regulator of muscle development, and its inactivation results in muscularity. The C-CRISPR system, utilizing multiple neighboring sgRNAs [...] Read more.

Hu sheep, an indigenous breed in China known for its high fecundity, are being studied to improve their growth and carcass traits. MSTN is a negative regulator of muscle development, and its inactivation results in muscularity. The C-CRISPR system, utilizing multiple neighboring sgRNAs targeting a key exon, has been successfully used to generate genes for complete knockout (KO) monkeys and mice in one step. In this study, the C-CRISPR system was used to generate MSTN-edited Hu sheep; 70 embryos injected with Cas9 mRNA and four sgRNAs targeting exon 3 of sheep MSTN were transferred to 13 recipients. Out of 10 lambs born from five recipients after full-term pregnancies, nine had complete MSTN KO with various mutations. No off-target effects were found. These MSTN-KO Hu sheep showed a double-muscled (DM) phenotype, characterized by a higher body weight at 3 and 4 months old, prominent muscular protrusion, clearly visible intermuscular groves, and muscle hypertrophy. The molecular analysis indicated enhanced AKT and suppressed ERK1/2 signaling in the gluteus muscle of the edited Hu sheep. In conclusion, MSTN complete KO Hu sheep with a DM phenotype were efficiently and specifically generated using C-CRISPR, and the C-CRISPR method is a promising tool for farm animal breeding. Full article

(This article belongs to the Special Issue Genetic Regulation of Animal Reproduction)

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12 pages, 932 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Assessment of Runs of Homozygosity by Whole-Genome Sequencing in Diverse Horse Breeds Worldwide

by Chujie Chen, Bo Zhu, Xiangwei Tang, Bin Chen, Mei Liu, Ning Gao, Sheng Li and Jingjing Gu

Genes 2023, 14(6), 1211; https://doi.org/10.3390/genes14061211 - 1 Jun 2023

Cited by 12 | Viewed by 3637

Abstract

In the genomes of diploid organisms, runs of homozygosity (ROH), consecutive segments of homozygosity, are extended. ROH can be applied to evaluate the inbreeding situation of individuals without pedigree data and to detect selective signatures via ROH islands. We sequenced and analyzed data [...] Read more.

In the genomes of diploid organisms, runs of homozygosity (ROH), consecutive segments of homozygosity, are extended. ROH can be applied to evaluate the inbreeding situation of individuals without pedigree data and to detect selective signatures via ROH islands. We sequenced and analyzed data derived from the whole-genome sequencing of 97 horses, investigated the distribution of genome-wide ROH patterns, and calculated ROH-based inbreeding coefficients for 16 representative horse varieties from around the world. Our findings indicated that both ancient and recent inbreeding occurrences had varying degrees of impact on various horse breeds. However, recent inbreeding events were uncommon, particularly among indigenous horse breeds. Consequently, the ROH-based genomic inbreeding coefficient could aid in monitoring the level of inbreeding. Using the Thoroughbred population as a case study, we discovered 24 ROH islands containing 72 candidate genes associated with artificial selection traits. We found that the candidate genes in Thoroughbreds were involved in neurotransmission (CHRNA6, PRKN, and GRM1), muscle development (ADAMTS15 and QKI), positive regulation of heart rate and heart contraction (HEY2 and TRDN), regulation of insulin secretion (CACNA1S, KCNMB2, and KCNMB3), and spermatogenesis (JAM3, PACRG, and SPATA6L). Our findings provide insight into horse breed characteristics and future breeding strategies. Full article

(This article belongs to the Special Issue Equine Genetics and Genomics)

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10 pages, 401 KiB

Open AccessEditor’s ChoiceArticle

Characteristics of Neuroimaging and Behavioural Phenotype in Polish Patients with PIGV-CDG—An Observational Study and Literature Review

by Michal Hutny, Patryk Lipinski and Aleksandra Jezela-Stanek

Genes 2023, 14(6), 1208; https://doi.org/10.3390/genes14061208 - 31 May 2023

Cited by 1 | Viewed by 2860

Abstract

Congenital disorders of glycosylation (CDGs) are a wide group of genetic diseases characterised by a severe clinical spectrum, consisting of developmental delays, dysmorphisms, and neurological deficits. Mutations in the PIGV gene lead to a disorder called hyperphosphatasia with impaired intellectual development syndrome 1 [...] Read more.

Congenital disorders of glycosylation (CDGs) are a wide group of genetic diseases characterised by a severe clinical spectrum, consisting of developmental delays, dysmorphisms, and neurological deficits. Mutations in the PIGV gene lead to a disorder called hyperphosphatasia with impaired intellectual development syndrome 1 (HPMRS1), distinct from other CDGs in terms of hyperphosphatemia related to abnormal ALP activity and brachytelephalangy. This article discusses the phenotype of six Polish patients with HPMRS1 with a special focus on behavioural and imaging features, which were not addressed in 26 previously reported cases. The medical records of six patients aged 6 to 22 years were collected and analysed. In all cases, the same PIGV homozygotic mutation (c.1022C>A; p.Ala341Glu) was found, although the patients presented a diverse spectrum of neurological and developmental disorders, concerning in most cases the muscular tonus and general developmental delay. The most prevalent dysmorphic features included hypertelorism, high palate, and finger anomalies, whereas other characteristics present in all previously described cases, such as a short, broad nose and brachytelephalangy, were less frequently observed. Similarly to previous reports, the magnetic resonance (MR) and computed tomography (CT) head scans returned varied results, including physiological and pathological brain images in equal measure, the latter of which consisted of cortical atrophy, delayed myelination, hydrocephalus, and hypoplastic corpus callosum. Each patient exhibited symptoms characteristic of autism spectrum disorders, especially in terms of attention deficits, as well as controlling and expressing emotions. The most common type of sensory processing disorder was over-responsivity. Despite the low prevalence of HPMRS1, the patients reported in the literature presented a rather uniform phenotype, which does not correspond with the one found in each individual of the studied group. Behavioural disorders and sensory impairment require additional care and awareness considering the global developmental delay often observed in these patients. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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11 pages, 274 KiB

Open AccessEditor’s ChoiceArticle

Associations between Lipid Profiles and Graves’ Orbitopathy can Be HLA-Dependent

by Magdalena Stasiak, Katarzyna Zawadzka-Starczewska, Bogusław Tymoniuk, Bartłomiej Stasiak and Andrzej Lewiński

Genes 2023, 14(6), 1209; https://doi.org/10.3390/genes14061209 - 31 May 2023

Cited by 5 | Viewed by 1804

Abstract

The risk of Graves’ orbitopathy (GO) is related to the human leukocyte antigen (HLA) profile and was demonstrated to be increased in patients with elevated total cholesterol (TC) and/or low-density lipoprotein (LDL) cholesterol. We hypothesized that there were some HLA alleles that were [...] Read more.

The risk of Graves’ orbitopathy (GO) is related to the human leukocyte antigen (HLA) profile and was demonstrated to be increased in patients with elevated total cholesterol (TC) and/or low-density lipoprotein (LDL) cholesterol. We hypothesized that there were some HLA alleles that were related to both GO and TC and/or LDL levels. Therefore, the aim of the study was to compare the TC/LDL results in patients in whom GO-related HLA alleles were present to those in whom they did not occur. HLA classes were genotyped using a next-generation sequencing method in 118 patients with Graves’ disease (GD), including 63 and 55 patients with and without GO, respectively. Lipid profiles were assessed at the time of the GD diagnosis. A significant correlation between the presence of GO high-risk alleles (HLA-B*37:01 and C*03:02) and higher TC/LDL levels was found. Additionally, the presence of alleles associated with non-GO GD (HLA-C*17:01 and B*08:01), as well as alleles in linkage disequilibrium with B*08:01 (i.e., HLA-DRB1*03:01 and DQB1*02:01), was correlated with lower TC levels. These results further confirm the significance of TC/LDL in the risk of GO development and provide evidence that associations between TC/LDL and GO can be HLA-dependent. Full article

(This article belongs to the Special Issue Genetics of Complex Human Disease)

27 pages, 5804 KiB

Open AccessEditor’s ChoiceArticle

Histone Deacetylases HD2A and HD2B Undergo Feedback Regulation by ABA and Modulate Drought Tolerance via Mediating ABA-Induced Transcriptional Repression

by Yongtao Han, Amira Haouel, Elisabeth Georgii, Santiago Priego-Cubero, Christoph J. Wurm, Daniel Hemmler, Philippe Schmitt-Kopplin, Claude Becker, Jörg Durner and Christian Lindermayr

Genes 2023, 14(6), 1199; https://doi.org/10.3390/genes14061199 - 30 May 2023

Cited by 8 | Viewed by 2714

Abstract

Histone deacetylation catalyzed by histone deacetylase plays a critical role in gene silencing and subsequently controls many important biological processes. It was reported that the expression of the plant-specific histone deacetylase subfamily HD2s is repressed by ABA in Arabidopsis. However, little is known [...] Read more.

Histone deacetylation catalyzed by histone deacetylase plays a critical role in gene silencing and subsequently controls many important biological processes. It was reported that the expression of the plant-specific histone deacetylase subfamily HD2s is repressed by ABA in Arabidopsis. However, little is known about the molecular relationship between HD2A/HD2B and ABA during the vegetative phase. Here, we describe that the hd2ahd2b mutant shows hypersensitivity to exogenous ABA during the germination and post-germination period. Additionally, transcriptome analyses revealed that the transcription of ABA-responsive genes was reprogrammed and the global H4K5ac level is specifically up-regulated in hd2ahd2b plants. ChIP-Seq and ChIP-qPCR results further verified that both HD2A and HD2B could directly and specifically bind to certain ABA-responsive genes. As a consequence, Arabidopsis hd2ahd2b plants displayed enhanced drought resistance in comparison to WT, which is consistent with increased ROS content, reduced stomatal aperture, and up-regulated drought-resistance-related genes. Moreover, HD2A and HD2B repressed ABA biosynthesis via the deacetylation of H4K5ac at NCED9. Taken together, our results indicate that HD2A and HD2B partly function through ABA signaling and act as negative regulators during the drought resistance response via the regulation of ABA biosynthesis and response genes. Full article

(This article belongs to the Special Issue Epigenetic and Transcriptomal Regulatory Mechanisms in ROS- and Phytohormone-Dependent Regulation of Plant Development)

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11 pages, 242 KiB

Open AccessEditor’s ChoiceReview

Whole Genome Resequencing Helps Study Important Traits in Chickens

by Xinwei Xiong, Jianxiang Liu and Yousheng Rao

Genes 2023, 14(6), 1198; https://doi.org/10.3390/genes14061198 - 30 May 2023

Cited by 14 | Viewed by 3715

Abstract

The emergence of high-throughput sequencing technology promotes life science development, provides technical support to analyze many life mechanisms, and presents new solutions to previously unsolved problems in genomic research. Resequencing technology has been widely used for genome selection and research on chicken population [...] Read more.

The emergence of high-throughput sequencing technology promotes life science development, provides technical support to analyze many life mechanisms, and presents new solutions to previously unsolved problems in genomic research. Resequencing technology has been widely used for genome selection and research on chicken population structure, genetic diversity, evolutionary mechanisms, and important economic traits caused by genome sequence differences since the release of chicken genome sequence information. This article elaborates on the factors influencing whole genome resequencing and the differences between these factors and whole genome sequencing. It reviews the important research progress in chicken qualitative traits (e.g., frizzle feather and comb), quantitative traits (e.g., meat quality and growth traits), adaptability, and disease resistance, and provides a theoretical basis to study whole genome resequencing in chickens. Full article

(This article belongs to the Special Issue Genetic Variation in Biological Traits)

21 pages, 5346 KiB

Open AccessEditor’s ChoiceArticle

Chromosome-Level Genome Assembly and Circadian Gene Repertoire of the Patagonia Blennie Eleginops maclovinus—The Closest Ancestral Proxy of Antarctic Cryonotothenioids

by Chi-Hing Christina Cheng, Angel G. Rivera-Colón, Bushra Fazal Minhas, Loralee Wilson, Niraj Rayamajhi, Luis Vargas-Chacoff and Julian M. Catchen

Genes 2023, 14(6), 1196; https://doi.org/10.3390/genes14061196 - 30 May 2023

Cited by 3 | Viewed by 2697

Abstract

The basal South American notothenioid Eleginops maclovinus (Patagonia blennie or róbalo) occupies a uniquely important phylogenetic position in Notothenioidei as the singular closest sister species to the Antarctic cryonotothenioid fishes. Its genome and the traits encoded therein would be the nearest representatives of [...] Read more.

The basal South American notothenioid Eleginops maclovinus (Patagonia blennie or róbalo) occupies a uniquely important phylogenetic position in Notothenioidei as the singular closest sister species to the Antarctic cryonotothenioid fishes. Its genome and the traits encoded therein would be the nearest representatives of the temperate ancestor from which the Antarctic clade arose, providing an ancestral reference for deducing polar derived changes. In this study, we generated a gene- and chromosome-complete assembly of the E. maclovinus genome using long read sequencing and HiC scaffolding. We compared its genome architecture with the more basally divergent Cottoperca gobio and the derived genomes of nine cryonotothenioids representing all five Antarctic families. We also reconstructed a notothenioid phylogeny using 2918 proteins of single-copy orthologous genes from these genomes that reaffirmed E. maclovinus’ phylogenetic position. We additionally curated E. maclovinus’ repertoire of circadian rhythm genes, ascertained their functionality by transcriptome sequencing, and compared its pattern of gene retention with C. gobio and the derived cryonotothenioids. Through reconstructing circadian gene trees, we also assessed the potential role of the retained genes in cryonotothenioids by referencing to the functions of the human orthologs. Our results found E. maclovinus to share greater conservation with the Antarctic clade, solidifying its evolutionary status as the direct sister and best suited ancestral proxy of cryonotothenioids. The high-quality genome of E. maclovinus will facilitate inquiries into cold derived traits in temperate to polar evolution, and conversely on the paths of readaptation to non-freezing habitats in various secondarily temperate cryonotothenioids through comparative genomic analyses. Full article

(This article belongs to the Special Issue Polar Genomics)

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17 pages, 1489 KiB

Open AccessEditor’s ChoiceReview

The Potential Role of Epigenetic Modifications on Different Facets in the Periodontal Pathogenesis

by Samuel Laberge, Daniel Akoum, Piotr Wlodarczyk, Jean-Daniel Massé, Dominique Fournier and Abdelhabib Semlali

Genes 2023, 14(6), 1202; https://doi.org/10.3390/genes14061202 - 30 May 2023

Cited by 8 | Viewed by 3724

Abstract

Periodontitis is a chronic inflammatory disease that affects the supporting structures of teeth. In the literature, the association between the pathogenicity of bacteria and environmental factors in this regard have been extensively examined. In the present study, we will shed light on the [...] Read more.

Periodontitis is a chronic inflammatory disease that affects the supporting structures of teeth. In the literature, the association between the pathogenicity of bacteria and environmental factors in this regard have been extensively examined. In the present study, we will shed light on the potential role that epigenetic change can play on different facets of its process, more particularly the modifications concerning the genes involved in inflammation, defense, and immune systems. Since the 1960s, the role of genetic variants in the onset and severity of periodontal disease has been widely demonstrated. These make some people more susceptible to developing it than others. It has been documented that the wide variation in its frequency for various racial and ethnic populations is due primarily to the complex interplay among genetic factors with those affecting the environment and the demography. In molecular biology, epigenetic modifications are defined as any change in the promoter for the CpG islands, in the structure of the histone protein, as well as post-translational regulation by microRNAs (miRNAs), being known to contribute to the alteration in gene expression for complex multifactorial diseases such as periodontitis. The key role of epigenetic modification is to understand the mechanism involved in the gene-environment interaction, and the development of periodontitis is now the subject of more and more studies that attempt to identify which factors are stimulating it, but also affect the reduced response to therapy. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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15 pages, 1851 KiB

Open AccessEditor’s ChoiceArticle

Clinical Heterogeneity and Different Phenotypes in Patients with SETD2 Variants: 18 New Patients and Review of the Literature

by Alejandro Parra, Rachel Rabin, John Pappas, Patricia Pascual, Mario Cazalla, Pedro Arias, Natalia Gallego-Zazo, Alfredo Santana, Ignacio Arroyo, Mercè Artigas, Harry Pachajoa, Yasemin Alanay, Ozlem Akgun-Dogan, Lyse Ruaud, Nathalie Couque, Jonathan Levy, Gloria Liliana Porras-Hurtado, Fernando Santos-Simarro, Maria Juliana Ballesta-Martinez, Encarna Guillén-Navarro, Hugo Muñoz-Hernández, Julián Nevado, Spanish OverGrowth Registry Initiative, Jair Tenorio-Castano and Pablo Lapunzina Show full author list Hide full author list

Genes 2023, 14(6), 1179; https://doi.org/10.3390/genes14061179 - 29 May 2023

Cited by 7 | Viewed by 4811

Abstract

SETD2 belongs to the family of histone methyltransferase proteins and has been associated with three nosologically distinct entities with different clinical and molecular features: Luscan–Lumish syndrome (LLS), intellectual developmental disorder, autosomal dominant 70 (MRD70), and Rabin–Pappas syndrome (RAPAS). LLS [MIM #616831] is an [...] Read more.

SETD2 belongs to the family of histone methyltransferase proteins and has been associated with three nosologically distinct entities with different clinical and molecular features: Luscan–Lumish syndrome (LLS), intellectual developmental disorder, autosomal dominant 70 (MRD70), and Rabin–Pappas syndrome (RAPAS). LLS [MIM #616831] is an overgrowth disorder with multisystem involvement including intellectual disability, speech delay, autism spectrum disorder (ASD), macrocephaly, tall stature, and motor delay. RAPAS [MIM #6201551] is a recently reported multisystemic disorder characterized by severely impaired global and intellectual development, hypotonia, feeding difficulties with failure to thrive, microcephaly, and dysmorphic facial features. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and potentially endocrine. Three patients who carried the missense variant p.Arg1740Gln in SETD2 were reported with a moderately impaired intellectual disability, speech difficulties, and behavioral abnormalities. More variable findings included hypotonia and dysmorphic features. Due to the differences with the two previous phenotypes, this association was then named intellectual developmental disorder, autosomal dominant 70 [MIM 620157]. These three disorders seem to be allelic and are caused either by loss-of-function, gain-of-function, or missense variants in the SETD2 gene. Here we describe 18 new patients with variants in SETD2, most of them with the LLS phenotype, and reviewed 33 additional patients with variants in SETD2 that have been previously reported in the scientific literature. This article offers an expansion of the number of reported individuals with LLS and highlights the clinical features and the similarities and differences among the three phenotypes associated with SETD2. Full article

(This article belongs to the Special Issue Molecular Basis of Rare Diseases)

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12 pages, 2969 KiB

Open AccessEditor’s ChoiceReview

ADAMTS Proteases: Importance in Animal Reproduction

by Pamela Hernández-Delgado, Monserrath Felix-Portillo and José A. Martínez-Quintana

Genes 2023, 14(6), 1181; https://doi.org/10.3390/genes14061181 - 29 May 2023

Cited by 13 | Viewed by 3204

Abstract

Many reproductive physiological processes, such as folliculogenesis, ovulation, implantation, and fertilization, require the synthesis, remodeling, and degradation of the extracellular matrix (ECM). The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family genes code for key metalloproteinases in the remodeling process of different [...] Read more.

Many reproductive physiological processes, such as folliculogenesis, ovulation, implantation, and fertilization, require the synthesis, remodeling, and degradation of the extracellular matrix (ECM). The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family genes code for key metalloproteinases in the remodeling process of different ECM. Several genes of this family encode for proteins with important functions in reproductive processes; in particular, ADAMTS1, 4, 5 and 9 are genes that are differentially expressed in cell types and the physiological stages of reproductive tissues. ADAMTS enzymes degrade proteoglycans in the ECM of the follicles so that the oocytes can be released and regulate follicle development during folliculogenesis, favoring the action of essential growth factors, such as FGF-2, FGF-7 and GDF-9. The transcriptional regulation of ADAMTS1 and 9 in preovulatory follicles occurs because of the gonadotropin surge in preovulatory follicles, via the progesterone/progesterone receptor complex. In addition, in the case of ADAMTS1, pathways involving protein kinase A (PKA), extracellular signal regulated protein kinase (ERK1/2) and the epidermal growth factor receptor (EGFR) might contribute to ECM regulation. Different Omic studies indicate the importance of genes of the ADAMTS family from a reproductive aspect. ADAMTS genes could serve as biomarkers for genetic improvement and contribute to enhance fertility and animal reproduction; however, more research related to these genes, the synthesis of proteins encoded by these genes, and regulation in farm animals is needed. Full article

(This article belongs to the Topic Application of Reproductive and Genomic Biotechnologies for Livestock Breeding and Selection)

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12 pages, 581 KiB

Open AccessEditor’s ChoiceArticle

Association between Aldosterone Synthase (CYP11B2) Gene Polymorphism and Hypertension in Pashtun Ethnic Population of Khyber Pakhtunkwha, Pakistan

by Waheed Ali Shah, Asif Jan, Muhammad Asghar Khan, Muhammad Saeed, Naveed Rahman, Zakiullah, Muhammad Sajjad Afridi, Fazli Khuda and Rani Akbar

Genes 2023, 14(6), 1184; https://doi.org/10.3390/genes14061184 - 29 May 2023

Cited by 10 | Viewed by 2899

Abstract

Genome-wide association studies significantly increased the number of hypertension risk variants; however, most of them focused on European societies. There is lack of such studies in developing countries, including Pakistan. The lack of research studies and the high prevalence of hypertension in the [...] Read more.

Genome-wide association studies significantly increased the number of hypertension risk variants; however, most of them focused on European societies. There is lack of such studies in developing countries, including Pakistan. The lack of research studies and the high prevalence of hypertension in the Pakistani community prompted us to design this study. Aldosterone synthase (CYP11B2) was thoroughly studied in different ethnic groups; however, no such study has been conducted in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. In essential hypertension, the aldosterone synthase gene (CYP11B2) plays a significant role. Aldosterone synthesis is affected by both hereditary and environmental factors. Aldosterone synthase (encoded by the CYP11B2 gene) controls the conversion of deoxycorticosterone to aldosterone and, thus, has genetic influences. Polymorphisms in the CYP11B2 gene are linked to an increased risk of hypertension. Previous research on the polymorphism of the aldosterone synthase (CYP11B2) gene and its relationship to hypertension produced inconclusive results. The present study investigates the relationship between CYP11B2 gene polymorphism and hypertension in Pakistan’s Pashtun population. We used the nascent exome sequencing method to identify variants associated with hypertension. The research was divided into two phases. In phase one, DNA samples from 200 adult hypertension patients (of age ≥ 30 years) and 200 controls were pooled (n = 200/pool) and subjected to Exome Sequencing. In the second phase, the WES reported SNPs were genotyped using the Mass ARRAY technique to verify and confirm the association between WES-identified SNPs and hypertension. WES identified a total of eight genetic variants in the CYP11B2 gene. The chi-square test and logistic regression analysis were used to estimate the minor allele frequencies (MAFs) and chosen SNPs relationships with hypertension. The frequency of minor allele T was found to be higher in cases compared to the control (42% vs. 30%: p = 0.001) for rs1799998 of CYP11B2 gene, while no significant results (p > 0.05) were observed for the remaining SNPs; rs4536, rs4537, rs4545, rs4543, rs4539, rs4546 and rs6418 showed no positive association with HTN in the studied population (all p > 0.05). Our study findings suggest that rs1799998 increases susceptibly to HTN in the Pashtun population of KP, Pakistan. Full article

(This article belongs to the Special Issue Genetics of Human Cardiovascular Disease)

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17 pages, 1191 KiB

Open AccessEditor’s ChoiceArticle

Genetic Diversity and Population Structure in Türkiye Bread Wheat Genotypes Revealed by Simple Sequence Repeats (SSR) Markers

by Aras Türkoğlu, Kamil Haliloğlu, Seyyed Abolgahasem Mohammadi, Ali Öztürk, Parisa Bolouri, Güller Özkan, Jan Bocianowski, Alireza Pour-Aboughadareh and Bita Jamshidi

Genes 2023, 14(6), 1182; https://doi.org/10.3390/genes14061182 - 29 May 2023

Cited by 14 | Viewed by 2983

Abstract

Wheat genotypes should be improved through available germplasm genetic diversity to ensure food security. This study investigated the molecular diversity and population structure of a set of Türkiye bread wheat genotypes using 120 microsatellite markers. Based on the results, 651 polymorphic alleles were [...] Read more.

Wheat genotypes should be improved through available germplasm genetic diversity to ensure food security. This study investigated the molecular diversity and population structure of a set of Türkiye bread wheat genotypes using 120 microsatellite markers. Based on the results, 651 polymorphic alleles were evaluated to determine genetic diversity and population structure. The number of alleles ranged from 2 to 19, with an average of 5.44 alleles per locus. Polymorphic information content (PIC) ranged from 0.031 to 0.915 with a mean of 0.43. In addition, the gene diversity index ranged from 0.03 to 0.92 with an average of 0.46. The expected heterozygosity ranged from 0.00 to 0.359 with a mean of 0.124. The unbiased expected heterozygosity ranged from 0.00 to 0.319 with an average of 0.112. The mean values of the number of effective alleles (Ne), genetic diversity of Nei (H) and Shannon’s information index (I) were estimated at 1.190, 1.049 and 0.168, respectively. The highest genetic diversity (GD) was estimated between genotypes G1 and G27. In the UPGMA dendrogram, the 63 genotypes were grouped into three clusters. The three main coordinates were able to explain 12.64, 6.38 and 4.90% of genetic diversity, respectively. AMOVA revealed diversity within populations at 78% and between populations at 22%. The current populations were found to be highly structured. Model-based cluster analyses classified the 63 genotypes studied into three subpopulations. The values of F-statistic (Fst) for the identified subpopulations were 0.253, 0.330 and 0.244, respectively. In addition, the expected values of heterozygosity (He) for these sub-populations were recorded as 0.45, 0.46 and 0.44, respectively. Therefore, SSR markers can be useful not only in genetic diversity and association analysis of wheat but also in its germplasm for various agronomic traits or mechanisms of tolerance to environmental stresses. Full article

(This article belongs to the Special Issue Genetic and Genomic Approaches for Breeding in Wheat)

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17 pages, 5311 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Characterization and Sequence Polymorphism Analyses of Glycine max Fibrillin (FBN) Revealed Its Role in Response to Drought Condition

by Muhammad Zeshan Zafer, Muhammad Hammad Nadeem Tahir, Zulqurnain Khan, Muhammad Sajjad, Xiangkuo Gao, Muhammad Amir Bakhtavar, Ummara Waheed, Maria Siddique, Zhide Geng and Shoaib Ur Rehman

Genes 2023, 14(6), 1188; https://doi.org/10.3390/genes14061188 - 29 May 2023

Cited by 4 | Viewed by 2222

Abstract

The fibrillin (FBN) gene family is widely distributed in all photosynthetic organisms. Members of this gene family are involved in plant growth and development and their response to various biotic and abiotic stress factors. In this study, 16 members of FBN [...] Read more.

The fibrillin (FBN) gene family is widely distributed in all photosynthetic organisms. Members of this gene family are involved in plant growth and development and their response to various biotic and abiotic stress factors. In this study, 16 members of FBN were identified in Glycine max and characterized by using different bioinformatics tools. Phylogenetic analysis classified FBN genes into seven groups. The presence of stress-related cis-elements in the upstream region of GmFBN highlighted their role in tolerance against abiotic stresses. To further decipher the function, physiochemical properties, conserved motifs, chromosomal localization, subcellular localization, and cis-acting regulatory elements were also analyzed. Gene expression analysis based on FPKM values revealed that GmFBNs greatly enhanced soybean drought tolerance and controlled the expression of several genes involved in drought response, except for GmFBN-4, GmFBN-5, GmFBN-6, GmFBN-7 and GmFBN-9. For high throughput genotyping, an SNP-based CAPS marker was also developed for the GmFBN-15 gene. The CAPS marker differentiated soybean genotypes based on the presence of either the GmFBN-15-G or GmFBN-15-A alleles in the CDS region. Association analysis showed that G. max accessions containing the GmFBN-15-A allele at the respective locus showed higher thousand seed weight compared to accessions containing the GmFBN-15-G allele. This research has provided the basic information to further decipher the function of FBN in soybean. Full article

(This article belongs to the Special Issue Genome-Wide Identifications: Recent Trends in Genomic Studies)

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12 pages, 3183 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification of NAC Gene Family and Expression Analysis under Abiotic Stresses in Avena sativa

by Lei Ling, Mingjing Li, Naiyu Chen, Xinying Xie, Zihui Han, Guoling Ren, Yajie Yin and Huixin Jiang

Genes 2023, 14(6), 1186; https://doi.org/10.3390/genes14061186 - 29 May 2023

Cited by 9 | Viewed by 2607

Abstract

In this study, a total of 177 NAC members were identified in Avena sativa, located on 21 chromosomes. Phylogenetic analysis showed that AsNAC proteins could be divided into seven subfamilies (I–VII), and that proteins in the same subfamily have similar protein motifs. Gene [...] Read more.

In this study, a total of 177 NAC members were identified in Avena sativa, located on 21 chromosomes. Phylogenetic analysis showed that AsNAC proteins could be divided into seven subfamilies (I–VII), and that proteins in the same subfamily have similar protein motifs. Gene structure analysis found that NAC introns ranged from 1 to 17. Cis-element analysis of the promoter indicated that the gene family may have stress-related elements and growth regulation elements. Through qRT-PCR experiments, we speculated that AsNACs genes can respond to abiotic stresses such as cold, freezing, salt, and saline alkali. This study provides a theoretical basis for further exploring the function of the NAC gene family in A. sativa. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Plants)

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21 pages, 1572 KiB

Open AccessEditor’s ChoiceReview

Peptides of a Feather: How Computation Is Taking Peptide Therapeutics under Its Wing

by Thomas David Daniel Kazmirchuk, Calvin Bradbury-Jost, Taylor Ann Withey, Tadesse Gessese, Taha Azad, Bahram Samanfar, Frank Dehne and Ashkan Golshani

Genes 2023, 14(6), 1194; https://doi.org/10.3390/genes14061194 - 29 May 2023

Cited by 19 | Viewed by 5137

Abstract

Leveraging computation in the development of peptide therapeutics has garnered increasing recognition as a valuable tool to generate novel therapeutics for disease-related targets. To this end, computation has transformed the field of peptide design through identifying novel therapeutics that exhibit enhanced pharmacokinetic properties [...] Read more.

Leveraging computation in the development of peptide therapeutics has garnered increasing recognition as a valuable tool to generate novel therapeutics for disease-related targets. To this end, computation has transformed the field of peptide design through identifying novel therapeutics that exhibit enhanced pharmacokinetic properties and reduced toxicity. The process of in-silico peptide design involves the application of molecular docking, molecular dynamics simulations, and machine learning algorithms. Three primary approaches for peptide therapeutic design including structural-based, protein mimicry, and short motif design have been predominantly adopted. Despite the ongoing progress made in this field, there are still significant challenges pertaining to peptide design including: enhancing the accuracy of computational methods; improving the success rate of preclinical and clinical trials; and developing better strategies to predict pharmacokinetics and toxicity. In this review, we discuss past and present research pertaining to the design and development of in-silico peptide therapeutics in addition to highlighting the potential of computation and artificial intelligence in the future of disease therapeutics. Full article

(This article belongs to the Topic Bioinformatics in Drug Design and Discovery)

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11 pages, 2724 KiB

Open AccessEditor’s ChoiceArticle

Methylation Levels in the Promoter Region of FHIT and PIAS1 Genes Associated with Mastitis Resistance in Xinjiang Brown Cattle

by Liwei Zhong, Shengchao Ma, Dan Wang, Menghua Zhang, Yuezhen Tian, Junmin He, Xiaoxue Zhang, Lei Xu, Cuiling Wu, Mingming Dong, Murong Gou, Xixia Huang and Kechuan Tian

Genes 2023, 14(6), 1189; https://doi.org/10.3390/genes14061189 - 29 May 2023

Cited by 8 | Viewed by 1972

Abstract

Mastitis causes serious economic losses in the dairy industry, but there are no effective treatments or preventive measures. In this study, the ZRANB3, PIAS1, ACTR3, LPCAT2, MGAT5, and SLC37A2 genes in Xinjiang brown cattle, which are associated with [...] Read more.

Mastitis causes serious economic losses in the dairy industry, but there are no effective treatments or preventive measures. In this study, the ZRANB3, PIAS1, ACTR3, LPCAT2, MGAT5, and SLC37A2 genes in Xinjiang brown cattle, which are associated with mastitis resistance, were identified using a GWAS. Pyrosequencing analysis showed that the promoter methylation levels of the FHIT and PIAS1 genes in the mastitis group were higher and lower, respectively, than those in the healthy group (65.97 ± 19.82% and 58.00 ± 23.52%). However, the methylation level of the PIAS1 gene promoter region in the mastitis group was lower than that in the healthy group (11.48 ± 4.12% and 12.17 ± 4.25%). Meanwhile, the methylation levels of CpG3, CpG5, CpG8, and CpG15 in the promoter region of the FHIT and PIAS1 genes in the mastitis group were significantly higher than those in the healthy group (p < 0.01), respectively. RT-qPCR showed that the expression levels of the FHIT and PIAS1 genes were significantly higher in the healthy group than those in the mastitis group (p < 0.01). Correlation analysis showed that the promoter methylation level of the FHIT gene was negatively correlated with its expression. Hence, increased methylation in the promoter of the FHIT gene reduces the mastitis resistance in Xinjiang brown cattle. Finally, this study provides a reference for the molecular-marker-assisted selection of mastitis resistance in dairy cattle. Full article

(This article belongs to the Special Issue Genetics and Breeding of Cattle)

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12 pages, 302 KiB

Open AccessEditor’s ChoiceArticle

Association of ACTN3 R577X Polymorphism with Elite Basketball Player Status and Training Responses

by Berkay Demirci, Celal Bulgay, Halil İbrahim Ceylan, Mehmet Ertuğrul Öztürk, Deniz Öztürk, Hasan Huseyin Kazan, Mehmet Ali Ergun, Mesut Cerit, Ekaterina A. Semenova, Andrey K. Larin, Edward V. Generozov, Ildus I. Ahmetov and Ladislav Cepicka

Genes 2023, 14(6), 1190; https://doi.org/10.3390/genes14061190 - 29 May 2023

Cited by 10 | Viewed by 4969

Abstract

The α-actinin-3 (ACTN3) gene rs1815739 (C/T, R577X) polymorphism is a variant frequently associated with athletic performance among different populations. However, there is limited research on the impact of this variant on athlete status and physical performance in basketball players. Therefore, the [...] Read more.

The α-actinin-3 (ACTN3) gene rs1815739 (C/T, R577X) polymorphism is a variant frequently associated with athletic performance among different populations. However, there is limited research on the impact of this variant on athlete status and physical performance in basketball players. Therefore, the aim of this study was twofold: (1) to determine the association of ACTN3 rs1815739 polymorphism with changes in physical performance in response to six weeks of training in elite basketball players using 30 m sprint and Yo-Yo Intermittent Recovery Test Level 2 (IR 2) tests, and (2) to compare ACTN3 genotype and allelic frequencies between elite basketball players and controls. The study included a total of 363 individuals, comprising 101 elite basketball players and 262 sedentary individuals. Genomic DNA was isolated from oral epithelial cells or leukocytes, and genotyping was performed by real-time PCR using KASP genotyping method or by microarray analysis. We found that the frequency of the ACTN3 rs1815739 XX genotype was significantly lower in basketball players compared to controls (10.9 vs. 21.4%, p = 0.023), suggesting that RR/RX genotypes were more favorable for playing basketball. Statistically significant (p = 0.045) changes were observed in Yo-Yo IRT 2 performance measurement tests in basketball players with the RR genotype only. In conclusion, our findings suggest that the carriage of the ACTN3 rs1815739 R allele may confer an advantage in basketball. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

17 pages, 5259 KiB

Open AccessEditor’s ChoiceArticle

Structural Characteristics and Phylogenetic Analysis of the Mitochondrial Genomes of Four Krisna Species (Hemiptera: Cicadellidae: Iassinae)

by Yanqiong Yang, Jiajia Wang, Renhuai Dai and Xianyi Wang

Genes 2023, 14(6), 1175; https://doi.org/10.3390/genes14061175 - 28 May 2023

Cited by 10 | Viewed by 2023

Abstract

Krisna species are insects that have piercing–sucking mouthparts and belong to the Krisnini tribe in the Iassinae subfamily of leafhoppers in the Cicadellidae family. In this study, we sequenced and compared the mitochondrial genomes (mitogenomes) of four Krisna species. The results showed that [...] Read more.

Krisna species are insects that have piercing–sucking mouthparts and belong to the Krisnini tribe in the Iassinae subfamily of leafhoppers in the Cicadellidae family. In this study, we sequenced and compared the mitochondrial genomes (mitogenomes) of four Krisna species. The results showed that all four mitogenomes were composed of cyclic double-stranded molecules and contained 13 protein-coding genes (PCGs) and 22 and 2 genes coding for tRNAs and rRNAs, respectively. Those mitogenomes exhibited similar base composition, gene size, and codon usage patterns for the protein-coding genes. The analysis of the nonsynonymous substitution rate (Ka)/synonymous substitution rate (Ks) showed that evolution occurred the fastest in ND4 and the slowest in COI. 13 PCGs that underwent purification selection were suitable for studying phylogenetic relationships within Krisna. ND2, ND6, and ATP6 had highly variable nucleotide diversity, whereas COI and ND1 exhibited the lowest diversity. Genes or gene regions with high nucleotide diversity can provide potential marker candidates for population genetics and species delimitation in Krisna. Analyses of parity and neutral plots showed that both natural selection and mutation pressure affected the codon usage bias. In the phylogenetic analysis, all subfamilies were restored to a monophyletic group; the Krisnini tribe is monophyletic, and the Krisna genus is paraphyletic. Our study provides novel insights into the significance of the background nucleotide composition and codon usage patterns in the CDSs of the 13 mitochondrial PCGs of the Krisna genome, which could enable the identification of a different gene organization and may be used for accurate phylogenetic analysis of Krisna species. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals)

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17 pages, 1646 KiB

Open AccessEditor’s ChoiceArticle

Association between HSPA8 Gene Variants and Ischemic Stroke: A Pilot Study Providing Additional Evidence for the Role of Heat Shock Proteins in Disease Pathogenesis

by Ksenia A. Kobzeva, Maria O. Soldatova, Tatiana A. Stetskaya, Vladislav O. Soldatov, Alexey V. Deykin, Maxim B. Freidin, Marina A. Bykanova, Mikhail I. Churnosov, Alexey V. Polonikov and Olga Y. Bushueva

Genes 2023, 14(6), 1171; https://doi.org/10.3390/genes14061171 - 27 May 2023

Cited by 12 | Viewed by 3298

Abstract

HSPA8 is involved in many stroke-associated cellular processes, playing a pivotal role in the protein quality control system. Here we report the results of the pilot study aimed at determining whether HSPA8 SNPs are linked to the risk of ischemic stroke (IS). DNA [...] Read more.

HSPA8 is involved in many stroke-associated cellular processes, playing a pivotal role in the protein quality control system. Here we report the results of the pilot study aimed at determining whether HSPA8 SNPs are linked to the risk of ischemic stroke (IS). DNA samples from 2139 Russians (888 IS patients and 1251 healthy controls) were genotyped for tagSNPs (rs1461496, rs10892958, and rs1136141) in the HSPA8 gene using probe-based PCR. SNP rs10892958 of HSPA8 was associated with an increased risk (risk allele G) of IS in smokers (OR = 1.37; 95% CI = 1.07–1.77; p = 0.01) and patients with low fruit and vegetable consumption (OR = 1.36; 95% CI = 1.14–1.63; p = 0.002). SNP rs1136141 of HSPA8 was also associated with an increased risk of IS (risk allele A) exclusively in smokers (OR = 1.68; 95% CI = 1.23–2.28; p = 0.0007) and in patients with a low fruit and vegetable intake (OR = 1.29; 95% CI = 1.05–1.60; p = 0.04). Sex-stratified analysis revealed an association of rs10892958 HSPA8 with an increased risk of IS in males (risk allele G; OR = 1.30; 95% CI = 1.05–1.61; p = 0.01). Thus, SNPs rs10892958 and rs1136141 in the HSPA8 gene represent novel genetic markers of IS. Full article

(This article belongs to the Special Issue Genetics of Human Cardiovascular Disease)

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16 pages, 677 KiB

Open AccessEditor’s ChoiceReview

The Role of Genetic and Epigenetic Regulation in Intestinal Fibrosis in Inflammatory Bowel Disease: A Descending Process or a Programmed Consequence?

by Sara Jarmakiewicz-Czaja, Aneta Sokal, Katarzyna Ferenc, Elżbieta Motyka, Kacper Helma and Rafał Filip

Genes 2023, 14(6), 1167; https://doi.org/10.3390/genes14061167 - 27 May 2023

Cited by 11 | Viewed by 2934

Abstract

Inflammatory bowel diseases (IBDs) are a group of chronic diseases characterized by recurring periods of exacerbation and remission. Fibrosis of the intestine is one of the most common complications of IBD. Based on current analyses, it is evident that genetic factors and mechanisms, [...] Read more.

Inflammatory bowel diseases (IBDs) are a group of chronic diseases characterized by recurring periods of exacerbation and remission. Fibrosis of the intestine is one of the most common complications of IBD. Based on current analyses, it is evident that genetic factors and mechanisms, as well as epigenetic factors, play a role in the induction and progression of intestinal fibrosis in IBD. Key genetic factors and mechanisms that appear to be significant include NOD2, TGF-β, TLRs, Il23R, and ATG16L1. Deoxyribonucleic acid (DNA) methylation, histone modification, and ribonucleic acid (RNA) interference are the primary epigenetic mechanisms. Genetic and epigenetic mechanisms, which seem to be important in the pathophysiology and progression of IBD, may potentially be used in targeted therapy in the future. Therefore, the aim of this study was to gather and discuss selected mechanisms and genetic factors, as well as epigenetic factors. Full article

(This article belongs to the Special Issue Genomics and Epigenomics of Gastrointestinal Disorders)

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20 pages, 2122 KiB

Open AccessEditor’s ChoiceReview

Microsatellite Instability and Immune Response: From Microenvironment Features to Therapeutic Actionability—Lessons from Colorectal Cancer

by Luana Greco, Federica Rubbino, Arianna Dal Buono and Luigi Laghi

Genes 2023, 14(6), 1169; https://doi.org/10.3390/genes14061169 - 27 May 2023

Cited by 20 | Viewed by 5013

Abstract

Microsatellite instability (MSI) can be found in 15–20% of all colorectal cancers (CRC) and is the key feature of a defective DNA mismatch repair (MMR) system. Currently, MSI has been established as a unique and pivotal biomarker in the diagnosis, prognosis, and treatment [...] Read more.

Microsatellite instability (MSI) can be found in 15–20% of all colorectal cancers (CRC) and is the key feature of a defective DNA mismatch repair (MMR) system. Currently, MSI has been established as a unique and pivotal biomarker in the diagnosis, prognosis, and treatment of CRC. MSI tumors display a strong lymphocytic activation and a shift toward a tumoral microenvironment restraining metastatic potential and ensuing in a high responsiveness to immunotherapy of MSI CRC. Indeed, neoplastic cells with an MMR defect overexpress several immune checkpoint proteins, such as programmed death-1 (PD-1) and programmed death-ligand 1(PD-L1), that can be pharmacologically targeted, allowing for the revival the cytotoxic immune response toward the tumor. This review aims to illustrate the role of MSI in the tumor biology of colorectal cancer, focusing on the immune interactions with the microenvironment and their therapeutic implications. Full article

(This article belongs to the Special Issue Genetics and Genomics of Gastrointestinal Cancers: From Prevention to Treatment)

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9 pages, 480 KiB

Open AccessEditor’s ChoiceArticle

Rett-like Phenotypes in HNRNPH2-Related Neurodevelopmental Disorder

by Joseph Nicho Gonzalez, Sylvie Goldman, Melissa T. Carter and Jennifer M. Bain

Genes 2023, 14(6), 1154; https://doi.org/10.3390/genes14061154 - 26 May 2023

Cited by 1 | Viewed by 3581

Abstract

Rett Syndrome (RTT) is a neurodevelopmental disorder with a prevalence of 1:10,000 to 15,000 females worldwide. Classic Rett Syndrome presents in early childhood with a period of developmental regression, loss of purposeful hand skills along with hand stereotypies, gait abnormalities, and loss of [...] Read more.

Rett Syndrome (RTT) is a neurodevelopmental disorder with a prevalence of 1:10,000 to 15,000 females worldwide. Classic Rett Syndrome presents in early childhood with a period of developmental regression, loss of purposeful hand skills along with hand stereotypies, gait abnormalities, and loss of acquired speech. Atypical RTT is diagnosed when a child shows some but not all the phenotypes of classic RTT, along with additional supporting criteria. Over 95% of classic RTT cases are attributed to pathogenic variants in Methyl-CpG Binding Protein 2 (MECP2), though additional genes have been implicated in other RTT cases, particularly those with the atypical RTT clinical picture. Other genetic etiologies have emerged with similar clinical characteristics to RTT Syndrome. Our team has characterized HNRNPH2-related neurodevelopmental disorder (HNRNPH2-RNDD) in 33 individuals associated with de novo pathogenic missense variants in the X-linked HNRNPH2 gene, characterized by developmental delay, intellectual disability, seizures, autistic-like features, and motor abnormalities. We sought to further characterize RTT clinical features in this group of individuals by using caregiver report. Twenty-six caregivers completed electronic surveys, with only 3 individuals having previously received an atypical RTT diagnosis, and no individuals with a typical RTT diagnosis. Caregivers reported a high number of behaviors and/or phenotypes consistent with RTT, including the major criteria of the syndrome, such as regression of developmental skills and abnormal gait. Based on the survey results, 12 individuals could meet the diagnostic clinical criteria for atypical RTT Syndrome. In summary, individuals with HNRNPH2-RNDD exhibit clinical characteristics that overlap with those of RTT, and therefore, HNRNPH2-RNDD, should be considered on the differential diagnosis list with this clinical picture. Full article

(This article belongs to the Special Issue Genetics of Rett Syndrome and Rett-Like Phenotypes: From Gene Discovery to Management and Treatment)

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20 pages, 2543 KiB

Open AccessEditor’s ChoiceArticle

Association of Gene Variants with Seasonal Variation in Muscle Strength and Aerobic Capacity in Elite Skiers

by Benedikt Gasser, Walter O. Frey, Paola Valdivieso, Johannes Scherr, Jörg Spörri and Martin Flück

Genes 2023, 14(6), 1165; https://doi.org/10.3390/genes14061165 - 26 May 2023

Cited by 2 | Viewed by 2423

Abstract

Background: The training of elite skiers follows a systematic seasonal periodization with a preparation period, when anaerobic muscle strength, aerobic capacity, and cardio-metabolic recovery are specifically conditioned to provide extra capacity for developing ski-specific physical fitness in the subsequent competition period. We hypothesized [...] Read more.

Background: The training of elite skiers follows a systematic seasonal periodization with a preparation period, when anaerobic muscle strength, aerobic capacity, and cardio-metabolic recovery are specifically conditioned to provide extra capacity for developing ski-specific physical fitness in the subsequent competition period. We hypothesized that periodization-induced alterations in muscle and metabolic performance demonstrate important variability, which in part is explained by gene-associated factors in association with sex and age. Methods: A total of 34 elite skiers (20.4 ± 3.1 years, 19 women, 15 men) underwent exhaustive cardiopulmonary exercise and isokinetic strength testing before and after the preparation and subsequent competition periods of the World Cup skiing seasons 2015–2018. Biometric data were recorded, and frequent polymorphisms in five fitness genes, ACE-I/D (rs1799752), TNC (rs2104772), ACTN3 (rs1815739), and PTK2 (rs7460, rs7843014), were determined with specific PCR reactions on collected DNA. Relative percentage changes of cardio-pulmonary and skeletal muscle metabolism and performance over the two seasonal periods were calculated for 160 data points and subjected to analysis of variance (ANOVA) to identify hypothesized and novel associations between performance alterations and the five respective genotypes and determine the influence of age × sex. A threshold of 0.1 for the effect size (h2) was deemed appropriate to identify relevant associations and motivate a post hoc test to localize effects. Results: The preparation and competition periods produced antidromic functional changes, the extent of which varied with increasing importance for anaerobic strength, aerobic performance, cardio-metabolic efficiency, and cardio-metabolic/muscle recovery. Only peak RER (−14%), but not anaerobic strength and peak aerobic performance, and parameters characterizing cardio-metabolic efficiency, differed between the first and last studied skiing seasons because improvements over the preparation period were mostly lost over the competition period. A number of functional parameters demonstrated associations of variability in periodic changes with a given genotype, and this was considerably influenced by athlete “age”, but not “sex”. This concerned age-dependent associations between periodic changes in muscle-related parameters, such as anaerobic strength for low and high angular velocities of extension and flexion and blood lactate concentration, with rs1799752 and rs2104772, whose gene products relate to sarcopenia. By contrast, the variance in period-dependent changes in body mass and peak VO2 with rs1799752 and rs2104772, respectively, was independent of age. Likely, the variance in periodic changes in the reliance of aerobic performance on lactate, oxygen uptake, and heart rate was associated with rs1815739 independent of age. These associations manifested at the post hoc level in genotype-associated differences in critical performance parameters. ACTN3 T-allele carriers demonstrated, compared to non-carriers, largely different periodic changes in the muscle-associated parameters of aerobic metabolism during exhaustive exercise, including blood lactate and respiration exchange ratio. The homozygous T-allele carriers of rs2104772 demonstrated the largest changes in extension strength at low angular velocity during the preparation period. Conclusions: Physiological characteristics of performance in skiing athletes undergo training period-dependent seasonal alterations the extent of which is largest for muscle metabolism-related parameters. Genotype associations for the variability in changes of aerobic metabolism-associated power output during exhaustive exercise and anaerobic peak power over the preparation and competition period motivate personalized training regimes. This may help to predict and maximize the benefit of physical conditioning of elite skiers based on chronological characteristics and the polymorphisms of the ACTN3, ACE, and TNC genes investigated here. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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16 pages, 3945 KiB

Open AccessEditor’s ChoiceArticle

Fecal Microbial Structure and Metabolic Profile in Post-Weaning Diarrheic Piglets

by Xianrui Zheng, Ke Nie, Yiliang Xu, Huibin Zhang, Fan Xie, Liming Xu, Zhiyong Zhang, Yueyun Ding, Zongjun Yin and Xiaodong Zhang

Genes 2023, 14(6), 1166; https://doi.org/10.3390/genes14061166 - 26 May 2023

Cited by 10 | Viewed by 2924

Abstract

(1) Background: Piglet diarrhea is one of the most serious diseases in pigs and has brought great economic losses to the pig industry. Alteration of the gut microbiota is an important factor in the etiology of piglet diarrhea. Therefore, this study aimed to [...] Read more.

(1) Background: Piglet diarrhea is one of the most serious diseases in pigs and has brought great economic losses to the pig industry. Alteration of the gut microbiota is an important factor in the etiology of piglet diarrhea. Therefore, this study aimed to analyze the differences in the gut microbial structures and fecal metabolic profile between post-weaning diarrhea and healthy Chinese Wannan Black pigs. (2) Methods: An integrated approach of 16S rRNA gene sequencing combined with LC/MS-based metabolomics was employed in this study. (3) Results: We found an increase in the relative abundance of the bacterial genus Campylobacter and a decrease in phylum Bacteroidetes and the species Streptococcus gallolyticus subsp. macedonicus. (S. macedonicus) in piglet diarrhea. Meanwhile, obvious changes in the fecal metabolic profile of diarrheic piglets were also detected, particularly higher levels of polyamines (spermine and spermidine). Moreover, there were substantial associations between the disturbed gut microbiota and the altered fecal metabolites, especially a strong positive relationship between spermidine and Campylobacter. (4) Conclusions: These observations may provide novel insights into potential etiologies related to post-weaning diarrhea and further enhance our understanding of the role of gut microbiota in host homeostasis and in modulating gut microbial structure. Full article

(This article belongs to the Special Issue Advances in Pig Breeding and Genetics)

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16 pages, 1485 KiB

Open AccessEditor’s ChoiceArticle

Genetic Mapping of Genotype-by-Ploidy Effects in Arabidopsis thaliana

by Cris L. Wijnen, Frank F. M. Becker, Andries A. Okkersen, C. Bastiaan de Snoo, Martin P. Boer, Fred A. van Eeuwijk, Erik Wijnker and Joost J. B. Keurentjes

Genes 2023, 14(6), 1161; https://doi.org/10.3390/genes14061161 - 26 May 2023

Cited by 2 | Viewed by 1979

Abstract

Plants can express different phenotypic responses following polyploidization, but ploidy-dependent phenotypic variation has so far not been assigned to specific genetic factors. To map such effects, segregating populations at different ploidy levels are required. The availability of an efficient haploid inducer line in [...] Read more.

Plants can express different phenotypic responses following polyploidization, but ploidy-dependent phenotypic variation has so far not been assigned to specific genetic factors. To map such effects, segregating populations at different ploidy levels are required. The availability of an efficient haploid inducer line in Arabidopsis thaliana allows for the rapid development of large populations of segregating haploid offspring. Because Arabidopsis haploids can be self-fertilised to give rise to homozygous doubled haploids, the same genotypes can be phenotyped at both the haploid and diploid ploidy level. Here, we compared the phenotypes of recombinant haploid and diploid offspring derived from a cross between two late flowering accessions to map genotype × ploidy (G × P) interactions. Ploidy-specific quantitative trait loci (QTLs) were detected at both ploidy levels. This implies that mapping power will increase when phenotypic measurements of monoploids are included in QTL analyses. A multi-trait analysis further revealed pleiotropic effects for a number of the ploidy-specific QTLs as well as opposite effects at different ploidy levels for general QTLs. Taken together, we provide evidence of genetic variation between different Arabidopsis accessions being causal for dissimilarities in phenotypic responses to altered ploidy levels, revealing a G × P effect. Additionally, by investigating a population derived from late flowering accessions, we revealed a major vernalisation-specific QTL for variation in flowering time, countering the historical bias of research in early flowering accessions. Full article

(This article belongs to the Special Issue Genetics and Breeding of Polyploid Plants)

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21 pages, 4188 KiB

Open AccessEditor’s ChoiceArticle

Genetic Diversity of Durum Wheat (Triticum turgidum L. ssp. durum, Desf) Germplasm as Revealed by Morphological and SSR Markers

by Temesgen Dagnaw, Behailu Mulugeta, Teklehaimanot Haileselassie, Mulatu Geleta, Rodomiro Ortiz and Kassahun Tesfaye

Genes 2023, 14(6), 1155; https://doi.org/10.3390/genes14061155 - 26 May 2023

Cited by 17 | Viewed by 5035

Abstract

Ethiopia is considered a center of origin and diversity for durum wheat and is endowed with many diverse landraces. This research aimed to estimate the extent and pattern of genetic diversity in Ethiopian durum wheat germplasm. Thus, 104 durum wheat genotypes representing thirteen [...] Read more.

Ethiopia is considered a center of origin and diversity for durum wheat and is endowed with many diverse landraces. This research aimed to estimate the extent and pattern of genetic diversity in Ethiopian durum wheat germplasm. Thus, 104 durum wheat genotypes representing thirteen populations, three regions, and four altitudinal classes were investigated for their genetic diversity, using 10 grain quality- and grain yield-related phenotypic traits and 14 simple sequence repeat (SSR) makers. The analysis of the phenotypic traits revealed a high mean Shannon diversity index (H′ = 0.78) among the genotypes and indicated a high level of phenotypic variation. The principal component analysis (PCA) classified the genotypes into three groups. The SSR markers showed a high mean value of polymorphic information content (PIC = 0.50) and gene diversity (h = 0.56), and a moderate number of alleles per locus (Na = 4). Analysis of molecular variance (AMOVA) revealed a high level of variation within populations, regions, and altitudinal classes, accounting for 88%, 97%, and 97% of the total variation, respectively. Pairwise genetic differentiation and Nei’s genetic distance analyses identified that the cultivars are distinct from the landrace populations. The distance-based (Discriminant Analysis of Principal Component (DAPC) and Minimum Spanning Network (MSN)) and model-based population stratification (STRUCTURE) methods of clustering grouped the genotypes into two clusters. Both the phenotypic data-based PCA and the molecular data-based DAPC and MSN analyses defined distinct groupings of cultivars and landraces. The phenotypic and molecular diversity analyses highlighted the high genetic variation in the Ethiopian durum wheat gene pool. The investigated SSRs showed significant associations with one or more target phenotypic traits. The markers identify landraces with high grain yield and quality traits. This study highlights the usefulness of Ethiopian landraces for cultivar development, contributing to food security in the region and beyond. Full article

(This article belongs to the Special Issue Genetics Studies on Wheat)

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23 pages, 6891 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification, Characterization and Expression Analysis of Plant Nuclear Factor (NF-Y) Gene Family Transcription Factors in Saccharum spp.

by Peter Swathik Clarancia, Murugan Naveenarani, Jayanarayanan Ashwin Narayan, Sakthivel Surya Krishna, Prathima Perumal Thirugnanasambandam, Ramanathan Valarmathi, Giriyapur Shivalingamurthy Suresha, Raju Gomathi, Raja Arun Kumar, Markandan Manickavasagam, Ramalingam Jegadeesan, Muthukrishnan Arun, Govindakurup Hemaprabha and Chinnaswamy Appunu

Genes 2023, 14(6), 1147; https://doi.org/10.3390/genes14061147 - 25 May 2023

Cited by 14 | Viewed by 3333

Abstract

Plant nuclear factor (NF-Y) is a transcriptional activating factor composed of three subfamilies: NF-YA, NF-YB, and NF-YC. These transcriptional factors are reported to function as activators, suppressors, and regulators under different developmental and stress conditions in plants. However, there is a lack of [...] Read more.

Plant nuclear factor (NF-Y) is a transcriptional activating factor composed of three subfamilies: NF-YA, NF-YB, and NF-YC. These transcriptional factors are reported to function as activators, suppressors, and regulators under different developmental and stress conditions in plants. However, there is a lack of systematic research on the NF-Y gene subfamily in sugarcane. In this study, 51 NF-Y genes (ShNF-Y), composed of 9 NF-YA, 18 NF-YB, and 24 NF-YC genes, were identified in sugarcane (Saccharum spp.). Chromosomal distribution analysis of ShNF-Ys in a Saccharum hybrid located the NF-Y genes on all 10 chromosomes. Multiple sequence alignment (MSA) of ShNF-Y proteins revealed conservation of core functional domains. Sixteen orthologous gene pairs were identified between sugarcane and sorghum. Phylogenetic analysis of NF-Y subunits of sugarcane, sorghum, and Arabidopsis showed that ShNF-YA subunits were equidistant while ShNF-YB and ShNF-YC subunits clustered distinctly, forming closely related and divergent groups. Expression profiling under drought treatment showed that NF-Y gene members were involved in drought tolerance in a Saccharum hybrid and its drought-tolerant wild relative, Erianthus arundinaceus. ShNF-YA5 and ShNF-YB2 genes had significantly higher expression in the root and leaf tissues of both plant species. Similarly, ShNF-YC9 had elevated expression in the leaf and root of E. arundinaceus and in the leaf of a Saccharum hybrid. These results provide valuable genetic resources for further sugarcane crop improvement programs. Full article

(This article belongs to the Special Issue Genome-Wide Identifications: Recent Trends in Genomic Studies)

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18 pages, 3843 KiB

Open AccessEditor’s ChoiceArticle

Complete Chloroplast Genome Determination of Ranunculus sceleratus from Republic of Korea (Ranunculaceae) and Comparative Chloroplast Genomes of the Members of the Ranunculus Genus

by Kang-Rae Kim, So Young Park, Heesoo Kim, Jeong Min Hong, Sun-Yu Kim and Jeong-Nam Yu

Genes 2023, 14(6), 1149; https://doi.org/10.3390/genes14061149 - 25 May 2023

Cited by 8 | Viewed by 2610

Abstract

Ranunculus sceleratus (family: Ranunculaceae) is a medicinally and economically important plant; however, gaps in taxonomic and species identification limit its practical applicability. This study aimed to sequence the chloroplast genome of R. sceleratus from Republic of Korea. Chloroplast sequences were compared and analyzed [...] Read more.

Ranunculus sceleratus (family: Ranunculaceae) is a medicinally and economically important plant; however, gaps in taxonomic and species identification limit its practical applicability. This study aimed to sequence the chloroplast genome of R. sceleratus from Republic of Korea. Chloroplast sequences were compared and analyzed among Ranunculus species. The chloroplast genome was assembled from Illumina HiSeq 2500 sequencing raw data. The genome was 156,329 bp and had a typical quadripartite structure comprising a small single-copy region, a large single-copy region, and two inverted repeats. Fifty-three simple sequence repeats were identified in the four quadrant structural regions. The region between the ndhC and trnV-UAC genes could be useful as a genetic marker to distinguish between R. sceleratus populations from Republic of Korea and China. The Ranunculus species formed a single lineage. To differentiate between Ranunculus species, we identified 16 hotspot regions and confirmed their potential using specific barcodes based on phylogenetic tree and BLAST-based analyses. The ndhE, ndhF, rpl23, atpF, rps4, and rpoA genes had a high posterior probability of codon sites in positive selection, while the amino acid site varied between Ranunculus species and other genera. Comparison of the Ranunculus genomes provides useful information regarding species identification and evolution that could guide future phylogenetic analyses. Full article

(This article belongs to the Topic Plant Chloroplast Genome and Evolution)

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13 pages, 10150 KiB

Open AccessEditor’s ChoiceArticle

Evaluating the Differential Response of Transcription Factors in Diploid versus Autotetraploid Rice Leaves Subjected to Diverse Saline–Alkali Stresses

by Ningning Wang, Yingkai Wang, Chenxi Wang, Zitian Leng, Fan Qi, Shiyan Wang, Yiming Zhou, Weilong Meng, Keyan Liu, Chunying Zhang and Jian Ma

Genes 2023, 14(6), 1151; https://doi.org/10.3390/genes14061151 - 25 May 2023

Cited by 2 | Viewed by 1722

Abstract

Saline–alkali stress is a significant abiotic stress factor that impacts plant growth, development, and crop yield. Consistent with the notion that genome-wide replication events can enhance plant stress resistance, autotetraploid rice exhibited a higher level of tolerance to saline–alkali stress than its donor [...] Read more.

Saline–alkali stress is a significant abiotic stress factor that impacts plant growth, development, and crop yield. Consistent with the notion that genome-wide replication events can enhance plant stress resistance, autotetraploid rice exhibited a higher level of tolerance to saline–alkali stress than its donor counterparts, which is reflected by differential gene expression between autotetraploid and diploid rice in response to salt, alkali, and saline–alkali stress. In this study, we investigated the expression of the transcription factors (TFs) in the leaf tissues of autotetraploid and diploid rice under different types of saline–alkali stress. Transcriptome analysis identified a total of 1040 genes from 55 TF families that were altered in response to these stresses, with a significantly higher number in autotetraploid rice compared to diploid rice. Contrarily, under these stresses, the number of expressed TF genes in autotetraploid rice was greater than that in diploid rice for all three types of stress. In addition to the different numbers, the differentially expressed TF genes were found to be from significantly distinct TF families between autotetraploid and diploid rice genotypes. The GO enrichment analysis unraveled that all the DEGs were distributed with differentially biological functions in rice, in particular those that were enriched in the pathways of phytohormones and salt resistance, signal transduction, and physiological and biochemical metabolism in autotetraploid rice compared to its diploid counterpart. This may provide useful guidance for studying the biological roles of polyploidization in plant resilience in response to saline–alkali stress. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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25 pages, 4291 KiB

Open AccessEditor’s ChoiceArticle

Phylogeny of the Diploid Species of Rubus (Rosaceae)

by Xin-Fen Gao, Xian-Hua Xiong, David E. Boufford, Yun-Dong Gao, Bo Xu and Cheng Zhang

Genes 2023, 14(6), 1152; https://doi.org/10.3390/genes14061152 - 25 May 2023

Cited by 11 | Viewed by 3474

Abstract

Rubus L. (Rosaceae, Rosoideae) contains around 700 species distributed on all continents except Antarctica, with the highest species diversity in temperate to subtropical regions of the northern hemisphere. The taxonomy of Rubus is challenging due to the frequency of polyploidy, hybridization and apomixis. [...] Read more.

Rubus L. (Rosaceae, Rosoideae) contains around 700 species distributed on all continents except Antarctica, with the highest species diversity in temperate to subtropical regions of the northern hemisphere. The taxonomy of Rubus is challenging due to the frequency of polyploidy, hybridization and apomixis. Previous studies mostly sampled sparsely and used limited DNA sequence data. The evolutionary relationships between infrageneric taxa, therefore, remain to be further clarified. In the present study, genotyping by sequencing (GBS) reduced-representation genome sequencing data from 186 accessions representing 65 species, 1 subspecies and 17 varieties of Rubus, with emphasis on diploid species, were used to infer a phylogeny using maximum likelihood and maximum parsimony methods. The major results were as follows: (1) we confirmed or reconfirmed the polyphyly or paraphyly of some traditionally circumscribed subgenera, sections and subsections; (2) 19 well-supported clades, which differed from one another on molecular, morphological and geographical grounds, were identified for the species sampled; (3) characteristics such as plants with dense bristles or not, leaves leathery or papyraceous, number of carpels, instead of inflorescences paniculate or not, aggregate fruits and leaves abaxially tomentose or not, may be of some use in classifying taxa whose drupelets are united into a thimble-shaped aggregate fruit that falls in its entirety from the dry receptacle; and (4) a preliminary classification scheme of diploid species of Rubus is proposed based on our results combined with those from previous phylogenetic analyses. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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13 pages, 2953 KiB

Open AccessEditor’s ChoiceArticle

Integration of Phosphoproteomics and Transcriptome Studies Reveals ABA Signaling Pathways Regulate UV-B Tolerance in Rhododendron chrysanthum Leaves

by Qi Sun, Xiangru Zhou, Liping Yang, Hongwei Xu and Xiaofu Zhou

Genes 2023, 14(6), 1153; https://doi.org/10.3390/genes14061153 - 25 May 2023

Cited by 10 | Viewed by 2140

Abstract

The influence of UV-B stress on the growth, development, and metabolism of alpine plants, such as the damage to DNA macromolecules, the decline in photosynthetic rate, and changes in growth, development, and morphology cannot be ignored. As an endogenous signal molecule, ABA demonstrates [...] Read more.

The influence of UV-B stress on the growth, development, and metabolism of alpine plants, such as the damage to DNA macromolecules, the decline in photosynthetic rate, and changes in growth, development, and morphology cannot be ignored. As an endogenous signal molecule, ABA demonstrates a wide range of responses to UV-B radiation, low temperature, drought, and other stresses. The typical effect of ABA on leaves is to reduce the loss of transpiration by closing the stomata, which helps plants resist abiotic and biological stress. The Changbai Mountains have a harsh environment, with low temperatures and thin air, so Rhododendron chrysanthum (R. chrysanthum) seedlings growing in the Changbai Mountains can be an important research object. In this study, a combination of physiological, phosphorylated proteomic, and transcriptomic approaches was used to investigate the molecular mechanisms by which abiotic stress leads to the phosphorylation of proteins in the ABA signaling pathway, and thereby mitigates UV-B radiation to R. chrysanthum. The experimental results show that a total of 12,289 differentially expressed genes and 109 differentially phosphorylated proteins were detected after UV-B stress in R. chrysanthum, mainly concentrated in plant hormone signaling pathways. Plants were treated with ABA prior to exposure to UV-B stress, and the results showed that ABA mitigated stomatal changes in plants, thus confirming the key role of endogenous ABA in plant adaptation to UV-B. We present a model that suggests a multifaceted R. chrysanthum response to UV-B stress, providing a theoretical basis for further elaboration of the mechanism of ABA signal transduction regulating stomata to resist UV-B radiation. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants: Present and Future)

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17 pages, 2946 KiB

Open AccessEditor’s ChoiceArticle

Identification and Interpretation of eQTL and eGenes for Hodgkin Lymphoma Susceptibility

by Yeeun An and Chaeyoung Lee

Genes 2023, 14(6), 1142; https://doi.org/10.3390/genes14061142 - 24 May 2023

Cited by 2 | Viewed by 2495

Abstract

Genome-wide association studies (GWAS) have revealed approximately 100 genomic signals associated with Hodgkin lymphoma (HL); however, their target genes and underlying mechanisms causing HL susceptibility remain unclear. In this study, transcriptome-wide analysis of expression quantitative trait loci (eQTL) was conducted to identify target [...] Read more.

Genome-wide association studies (GWAS) have revealed approximately 100 genomic signals associated with Hodgkin lymphoma (HL); however, their target genes and underlying mechanisms causing HL susceptibility remain unclear. In this study, transcriptome-wide analysis of expression quantitative trait loci (eQTL) was conducted to identify target genes associated with HL GWAS signals. A mixed model, which explains polygenic regulatory effects by the genomic covariance among individuals, was implemented to discover expression genes (eGenes) using genotype data from 462 European/African individuals. Overall, 80 eGenes were identified to be associated with 20 HL GWAS signals. Enrichment analysis identified apoptosis, immune responses, and cytoskeletal processes as functions of these eGenes. The eGene of rs27524 encodes ERAP1 that can cleave peptides attached to human leukocyte antigen in immune responses; its minor allele may help Reed–Sternberg cells to escape the immune response. The eGene of rs7745098 encodes ALDH8A1 that can oxidize the precursor of acetyl-CoA for the production of ATP; its minor allele may increase oxidization activity to evade apoptosis of pre-apoptotic germinal center B cells. Thus, these minor alleles may be genetic risk factors for HL susceptibility. Experimental studies on genetic risk factors are needed to elucidate the underlying mechanisms of HL susceptibility and improve the accuracy of precision oncology. Full article

(This article belongs to the Section Bioinformatics)

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9 pages, 481 KiB

Open AccessEditor’s ChoiceArticle

Longitudinal Analysis of Contrasts in Gene Expression Data

by Georg Hahn, Tanya Novak, Jeremy C. Crawford, Adrienne G. Randolph and Christoph Lange

Genes 2023, 14(6), 1134; https://doi.org/10.3390/genes14061134 - 24 May 2023

Cited by 1 | Viewed by 1678

Abstract

We are interested in detecting a departure from the baseline in a longitudinal analysis in the context of multiple organ dysfunction syndrome (MODS). In particular, we are given gene expression reads at two time points for a fixed number of genes and individuals. [...] Read more.

We are interested in detecting a departure from the baseline in a longitudinal analysis in the context of multiple organ dysfunction syndrome (MODS). In particular, we are given gene expression reads at two time points for a fixed number of genes and individuals. The individuals can be subdivided into two groups, denoted as groups A and B. Using the two time points, we compute a contrast of gene expression reads per individual and gene. The age of each individual is known and it is used to compute, for each gene separately, a linear regression of the gene expression contrasts on the individual’s age. Looking at the intercept of the linear regression to detect a departure from the baseline, we aim to reliably single out those genes for which there is a difference in the intercept among those individuals in group A and not in group B. In this work, we develop testing methodology for this setting based on two hypothesis tests—one under the null and one under an appropriately formulated alternative. We demonstrate the validity of our approach using a dataset created by bootstrapping from a real data application in the context of multiple organ dysfunction syndrome (MODS). Full article

(This article belongs to the Section Bioinformatics)

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10 pages, 2062 KiB

Open AccessEditor’s ChoiceCommunication

Development and Validation of a 54K Genome-Wide Liquid SNP Chip Panel by Target Sequencing for Dairy Goat

by Shengyu Guan, Weining Li, Hai Jin, Lu Zhang and Guoshi Liu

Genes 2023, 14(5), 1122; https://doi.org/10.3390/genes14051122 - 22 May 2023

Cited by 14 | Viewed by 3807

Abstract

As an important genotyping platform, SNP chips are essential for implementing genomic selection. In this article, we introduced the development of a liquid SNP chip panel for dairy goats. This panel contains 54,188 SNPs based on genotyping by targeted sequencing (GBTS) technology. The [...] Read more.

As an important genotyping platform, SNP chips are essential for implementing genomic selection. In this article, we introduced the development of a liquid SNP chip panel for dairy goats. This panel contains 54,188 SNPs based on genotyping by targeted sequencing (GBTS) technology. The source of SNPs in the panel were from the whole-genome resequencing of 110 dairy goats from three European and two Chinese indigenous dairy goat breeds. The performance of this liquid SNP chip panel was evaluated by genotyping 200 additional goats. Fifteen of them were randomly selected for whole-genome resequencing. The average capture ratio of the panel design loci was 98.41%, and the genotype concordance with resequencing reached 98.02%. We further used this chip panel to conduct genome-wide association studies (GWAS) to detect genetic loci that affect coat color in dairy goats. A single significant association signal for hair color was found on chromosome 8 at 31.52–35.02 Mb. The TYRP1 gene, which is associated with coat color in goats, was identified to be located at this genomic region (chromosome 8: 31,500,048-31,519,064). The emergence of high-precision and low-cost liquid microarrays will improve the analysis of genomics and breeding efficiency of dairy goats. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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